2024/12/14 更新

写真a

タニウチ シュウスケ
谷内 秀輔
TANIUCHI Shusuke
所属
医学部 医学科 基礎医学講座 薬理学講座
外部リンク

学位

  • 博士(理学) ( 2011年9月   岡山大学 )

研究キーワード

  • 低酸素応答

  • 小胞体ストレス応答

  • 糖尿病

  • 視床下部

  • 下垂体

  • 分子内分泌学

  • 統合的ストレス応答

  • 小胞体ストレス

  • 低酸素

研究分野

  • ライフサイエンス / 病態医化学

学歴

  • 岡山大学   大学院自然科学研究科   博士後期課程 バイオサイエンス専攻

    2007年4月 - 2011年9月

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  • 岡山大学   大学院自然科学研究科   博士前期課程 生物科学専攻

    2005年4月 - 2007年3月

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  • 岡山大学   理学部   生物学科

    2001年4月 - 2005年3月

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経歴

  • 旭川医科大学   薬理学講座   助教

    2021年5月 - 現在

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  • 徳島大学   先端酵素学研究所 プロテオゲノム研究領域 生体機能学分野   特任研究員

    2016年4月 - 2021年4月

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  • 徳島大学   疾患プロテオゲノム研究センター 生体機能分野   特任研究員

    2014年5月 - 2016年3月

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  • 広島大学   大学院総合科学研究科 脳科学分野   博士研究員

    2011年10月 - 2014年3月

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  • 日本学術振興会   特別研究員(DC2)

    2009年4月 - 2011年3月

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所属学協会

  • 日本プロテオーム学会

    2021年6月 - 現在

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  • 日本生化学会

    2015年 - 現在

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  • 日本臨床ストレス応答学会

    2014年 - 現在

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  • 日本神経内分泌学会

    2013年 - 現在

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  • 日本比較内分泌学会

    2005年 - 現在

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委員歴

  • 旭川医科大学   遺伝子組換え実験安全委員会 安全主任者  

    2023年10月 - 現在   

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  • 旭川医科大学   病原体等安全管理委員会 委員  

    2023年10月 - 現在   

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論文

  • The ATF6β-calreticulin axis promotes neuronal survival under endoplasmic reticulum stress and excitotoxicity. 査読 国際誌

    Dinh Thi Nguyen, Thuong Manh Le, Tsuyoshi Hattori, Mika Takarada-Iemata, Hiroshi Ishii, Jureepon Roboon, Takashi Tamatani, Takayuki Kannon, Kazuyoshi Hosomichi, Atsushi Tajima, Shusuke Taniuchi, Masato Miyake, Seiichi Oyadomari, Takashi Tanaka, Nobuo Kato, Shunsuke Saito, Kazutoshi Mori, Osamu Hori

    Scientific reports   11 ( 1 )   13086 - 13086   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    While ATF6α plays a central role in the endoplasmic reticulum (ER) stress response, the function of its paralogue ATF6β remains elusive, especially in the central nervous system (CNS). Here, we demonstrate that ATF6β is highly expressed in the hippocampus of the brain, and specifically regulates the expression of calreticulin (CRT), a molecular chaperone in the ER with a high Ca2+-binding capacity. CRT expression was reduced to ~ 50% in the CNS of Atf6b-/- mice under both normal and ER stress conditions. Analysis using cultured hippocampal neurons revealed that ATF6β deficiency reduced Ca2+ stores in the ER and enhanced ER stress-induced death. The higher levels of death in Atf6b-/- neurons were recovered by ATF6β and CRT overexpressions, or by treatment with Ca2+-modulating reagents such as BAPTA-AM and 2-APB, and with an ER stress inhibitor salubrinal. In vivo, kainate-induced neuronal death was enhanced in the hippocampi of Atf6b-/- and Calr+/- mice, and restored by administration of 2-APB and salubrinal. These results suggest that the ATF6β-CRT axis promotes neuronal survival under ER stress and excitotoxity by improving intracellular Ca2+ homeostasis.

    DOI: 10.1038/s41598-021-92529-w

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  • Nanosecond pulsed electric fields induce the integrated stress response via reactive oxygen species-mediated heme-regulated inhibitor (HRI) activation. 査読 国際誌

    Yoshimasa Hamada, Yuji Furumoto, Akira Izutani, Shusuke Taniuchi, Masato Miyake, Miho Oyadomari, Kenji Teranishi, Naoyuki Shimomura, Seiichi Oyadomari

    PloS one   15 ( 3 )   e0229948   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The integrated stress response (ISR) is one of the most important cytoprotective mechanisms and is integrated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Four eIF2α kinases, heme-regulated inhibitor (HRI), double-stranded RNA-dependent protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), and general control nonderepressible 2 (GCN2), are activated in response to several stress conditions. We previously reported that nanosecond pulsed electric fields (nsPEFs) are a potential therapeutic tool for ISR activation. In this study, we examined which eIF2α kinase is activated by nsPEF treatment. To assess the responsible eIF2α kinase, we used previously established eIF2α kinase quadruple knockout (4KO) and single eIF2α kinase-rescued 4KO mouse embryonic fibroblast (MEF) cells. nsPEFs 70 ns in duration with 30 kV/cm electric fields caused eIF2α phosphorylation in wild-type (WT) MEF cells. On the other hand, nsPEF-induced eIF2α phosphorylation was completely abolished in 4KO MEF cells and was recovered by HRI overexpression. CM-H2DCFDA staining showed that nsPEFs generated reactive oxygen species (ROS), which activated HRI. nsPEF-induced eIF2α phosphorylation was blocked by treatment with the ROS scavenger N-acetyl-L-cysteine (NAC). Our results indicate that the eIF2α kinase HRI is responsible for nsPEF-induced ISR activation and is activated by nsPEF-generated ROS.

    DOI: 10.1371/journal.pone.0229948

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  • Cell-based HTS identifies a chemical chaperone for preventing ER protein aggregation and proteotoxicity. 査読 国際誌

    Keisuke Kitakaze, Shusuke Taniuchi, Eri Kawano, Yoshimasa Hamada, Masato Miyake, Miho Oyadomari, Hirotatsu Kojima, Hidetaka Kosako, Tomoko Kuribara, Suguru Yoshida, Takamitsu Hosoya, Seiichi Oyadomari

    eLife   8   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The endoplasmic reticulum (ER) is responsible for folding secretory and membrane proteins, but disturbed ER proteostasis may lead to protein aggregation and subsequent cellular and clinical pathologies. Chemical chaperones have recently emerged as a potential therapeutic approach for ER stress-related diseases. Here, we identified 2-phenylimidazo[2,1-b]benzothiazole derivatives (IBTs) as chemical chaperones in a cell-based high-throughput screen. Biochemical and chemical biology approaches revealed that IBT21 directly binds to unfolded or misfolded proteins and inhibits protein aggregation. Finally, IBT21 prevented cell death caused by chemically induced ER stress and by a proteotoxin, an aggression-prone prion protein. Taken together, our data show the promise of IBTs as potent chemical chaperones that can ameliorate diseases resulting from protein aggregation under ER stress.

    DOI: 10.7554/eLife.43302

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  • Concomitant Nrf2- and ATF4-activation by Carnosic Acid Cooperatively Induces Expression of Cytoprotective Genes. 査読 国際誌

    Junsei Mimura, Atsushi Inose-Maruyama, Shusuke Taniuchi, Kunio Kosaka, Hidemi Yoshida, Hiromi Yamazaki, Shuya Kasai, Nobuhiko Harada, Randal J Kaufman, Seiichi Oyadomari, Ken Itoh

    International journal of molecular sciences   20 ( 7 )   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    : Carnosic acid (CA) is a phytochemical found in some dietary herbs, such as Rosmarinus officinalis L., and possesses antioxidative and anti-microbial properties. We previously demonstrated that CA functions as an activator of nuclear factor, erythroid 2 (NF-E2)-related factor 2 (Nrf2), an oxidative stress-responsive transcription factor in human and rodent cells. CA enhances the expression of nerve growth factor (NGF) and antioxidant genes, such as HO-1 in an Nrf2-dependent manner in U373MG human astrocytoma cells. However, CA also induces NGF gene expression in an Nrf2-independent manner, since 50 μM of CA administration showed striking NGF gene induction compared with the classical Nrf2 inducer tert-butylhydroquinone (tBHQ) in U373MG cells. By comparative transcriptome analysis, we found that CA activates activating transcription factor 4 (ATF4) in addition to Nrf2 at high doses. CA activated ATF4 in phospho-eIF2α- and heme-regulated inhibitor kinase (HRI)-dependent manners, indicating that CA activates ATF4 through the integrated stress response (ISR) pathway. Furthermore, CA activated Nrf2 and ATF4 cooperatively enhanced the expression of NGF and many antioxidant genes while acting independently to certain client genes. Taken together, these results represent a novel mechanism of CA-mediated gene regulation evoked by Nrf2 and ATF4 cooperation.

    DOI: 10.3390/ijms20071706

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  • Chronic subcutaneous infusion of neurosecretory protein GM increases body mass gain in chicks. 査読 国際誌

    Kenshiro Shikano, Shusuke Taniuchi, Eiko Iwakoshi-Ukena, Megumi Furumitsu, George E Bentley, Lance J Kriegsfeld, Kazuyoshi Ukena

    General and comparative endocrinology   265   71 - 76   2018年9月

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    記述言語:英語  

    Recently we discovered a small hypothalamic protein in the chicken, named neurosecretory protein GL (NPGL), which is associated with body growth and energy metabolism in birds and rodents. Genome database analysis suggested that the NPGL gene has a paralogous gene in vertebrates, named neurosecretory protein GM (NPGM). However, the biological action of NPGM remains unclear. In this study, we investigated whether NPGM affects body growth in chicks. We found that subcutaneous infusion of NPGM for six days increased body mass gain in a dose-dependent manner. Despite the observed increase in body mass, infusion of NPGM did not alter food and water intake. Of note, we observed tendency of mass increase of several peripheral tissues, specifically. When we compared several tissue types, NPGM seemed to induce the largest growth increase in white adipose tissue mass. These results suggest that NPGM may accelerate fat accumulation and body growth. In addition, we analyzed whether NPGM increases body growth through the action of pituitary hormones. However, we observed no significant changes in mRNA expression of pituitary hormones or plasma levels of growth hormone in NPGM-treated chicks. This is the first report describing the biological action of NPGM in vertebrates.

    DOI: 10.1016/j.ygcen.2017.11.010

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  • Erratum: Author Correction: Localization and function of neurosecretory protein GM, a novel small secretory protein, in the chicken hypothalamus (Scientific reports (2018) 8 1 (704))

    Kenshiro Shikano, Yuki Bessho, Masaki Kato, Eiko Iwakoshi-Ukena, Shusuke Taniuchi, Megumi Furumitsu, Tetsuya Tachibana, George E. Bentley, Lance J. Kriegsfeld, Kazuyoshi Ukena

    Scientific reports   8 ( 1 )   6235   2018年4月

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    掲載種別:研究論文(学術雑誌)  

    A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

    DOI: 10.1038/s41598-018-24103-w

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  • PERK-mediated translational control is required for collagen secretion in chondrocytes. 査読 国際誌

    Satoshi Hisanaga, Masato Miyake, Shusuke Taniuchi, Miho Oyadomari, Masatoshi Morimoto, Ryosuke Sato, Jun Hirose, Hiroshi Mizuta, Seiichi Oyadomari

    Scientific reports   8 ( 1 )   773 - 773   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    As chondrocytes are highly secretory and they experience a variety of stresses, physiological unfolded protein response (UPR) signalling is essential for extracellular matrix (ECM) secretion and chondrogenesis. In the three branches of the UPR pathway, PERK governs the translational attenuation and transcriptional upregulation of amino acid and redox metabolism and induction of apoptosis. It was previously demonstrated that a defect of the PERK branch of the UPR signalling pathway causes the accumulation of unfolded proteins, leading to cell death without perturbing endoplasmic reticulum (ER)-to-Golgi transport in pancreatic β cells. However, little is known about the role of PERK in chondrocytes. In this study, we found that PERK signalling is activated in chondrocytes, and inhibition of PERK reduces collagen secretion despite causing excessive collagen synthesis in the ER. Perk -/- mice displayed reduced collagen in articular cartilage but no differences in chondrocyte proliferation or apoptosis compared to the findings in wild-type mice. PERK inhibition increases misfolded protein levels in the ER, which largely hinder ER-to-Golgi transport. These results suggest that the translational control mediated by PERK is a critical determinant of ECM secretion in chondrocytes.

    DOI: 10.1038/s41598-017-19052-9

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  • Localization and function of neurosecretory protein GM, a novel small secretory protein, in the chicken hypothalamus. 査読 国際誌

    Kenshiro Shikano, Yuki Bessho, Masaki Kato, Eiko Iwakoshi-Ukena, Shusuke Taniuchi, Megumi Furumitsu, Tetsuya Tachibana, George E Bentley, Lance J Kriegsfeld, Kazuyoshi Ukena

    Scientific reports   8 ( 1 )   704 - 704   2018年1月

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    記述言語:英語  

    Recently, we discovered a novel cDNA encoding the precursor of a small secretory protein, neurosecretory protein GL (NPGL), in the hypothalamic infundibulum of chickens. NPGL plays an important role in the regulation of growth and feeding. A database search indicated that the NPGL gene has a paralogous gene: neurosecretory protein GM (NPGM), also in chickens. We identified cDNA encoding the NPGM precursor in chickens. Morphological analysis showed that NPGM-containing cells are specifically localized in the medial mammillary nucleus (MM) and infundibular nucleus (IN) in the hypothalamus. In addition, we found that NPGM and NPGL are co-localized, especially in the MM. The expression levels of NPGM mRNA gradually decreased during post-hatch development, in contrast to those of NPGL mRNA. Moreover, we investigated the relationship between NPGM and other known factors. NPGM was found to be produced in histaminergic neurons in the MM. NPGM and histidine decarboxylase, a histamine-producing enzyme, displayed similar expression patterns during post-hatch development. Acute intracerebroventricular injection of NPGM decreased food intake, similar to the effect of histamine. To our knowledge, this is the first report of the localization and function of NPGM in the brain of vertebrates. These results will further advance the understanding mechanisms underlying energy homeostasis.

    DOI: 10.1038/s41598-017-18822-9

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  • Neurosecretory protein GL stimulates food intake, de novo lipogenesis, and onset of obesity. 査読 国際誌

    Eiko Iwakoshi-Ukena, Kenshiro Shikano, Kunihiro Kondo, Shusuke Taniuchi, Megumi Furumitsu, Yuta Ochi, Tsutomu Sasaki, Shiki Okamoto, George E Bentley, Lance J Kriegsfeld, Yasuhiko Minokoshi, Kazuyoshi Ukena

    eLife   6   2017年8月

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    記述言語:英語  

    Mechanisms underlying the central regulation of food intake and fat accumulation are not fully understood. We found that neurosecretory protein GL (NPGL), a newly-identified neuropeptide, increased food intake and white adipose tissue (WAT) in rats. NPGL-precursor gene overexpression in the hypothalamus caused increases in food intake, WAT, body mass, and circulating insulin when fed a high calorie diet. Intracerebroventricular administration of NPGL induced de novo lipogenesis in WAT, increased insulin, and it selectively induced carbohydrate intake. Neutralizing antibody administration decreased the size of lipid droplets in WAT. Npgl mRNA expression was upregulated by fasting and low insulin levels. Additionally, NPGL-producing cells were responsive to insulin. These results point to NPGL as a novel neuronal regulator that drives food intake and fat deposition through de novo lipogenesis and acts to maintain steady-state fat level in concert with insulin. Dysregulation of NPGL may be a root cause of obesity.

    DOI: 10.7554/eLife.28527

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  • Runx3 transcription factor regulates ovarian functions and ovulation in female mice. 査読

    Fumiya Ojima, Yuka Saito, Yukiko Tsuchiya, Daichi Kayo, Syusuke Taniuchi, Maho Ogoshi, Hiroshi Fukamachi, Sakae Takeuchi, Sumio Takahashi

    The Journal of reproduction and development   62 ( 5 )   479 - 486   2016年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We previously demonstrated that the Runx3 transcription factor is expressed in the hypothalami, pituitaries, and ovaries of mice, and that Runx3 knockout (Runx3-/-) mice are anovulatory and their uteri are atrophic. Runx3 mRNA expression was detected in the granulosa cells of ovarian follicles, and in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). In the present study, we examined the effects of Runx3 knockout on the gene expression of enzymes associated with steroidogenesis. We found decreased Cyp11a1 mRNA expression in Runx3-/- mouse ovaries compared with that in wild-type (wt) mouse ovaries at the age of 8 weeks. In situ hybridization analysis showed that the percentages of Cyp11a1 mRNA-expressing theca cells in follicles of Runx3-/- mice were decreased compared with those of wt mice. In accord with the alterations in Runx3-/- mouse ovaries, Kiss1 mRNA levels in ARC were increased, whereas mRNA levels of kisspeptin in AVPV were decreased, and gonadotropin-releasing hormone in the preoptic area and follicle-stimulating hormone β subunit gene were increased in Runx3-/- mice. Following an ovarian transplantation experiment between Runx3-/- mice and wt mice, corpora lutea were observed when ovaries from Runx3-/- mice were transplanted into wt mice, but not when those from wt mice were transplanted into Runx3-/- mice, suggesting that Runx3 in the hypothalamo-pituitary system may drive gonadotropin release to induce ovulation in the ovary. These findings indicate that Runx3 plays a crucial role in the hypothalamo-pituitary-gonadal axis.

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  • Integrated stress response of vertebrates is regulated by four eIF2α kinases. 査読 国際誌

    Shusuke Taniuchi, Masato Miyake, Kazue Tsugawa, Miho Oyadomari, Seiichi Oyadomari

    Scientific reports   6   32886 - 32886   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The integrated stress response (ISR) is a cytoprotective pathway initiated upon phosphorylation of the eukaryotic translation initiation factor 2 (eIF2α) residue designated serine-51, which is critical for translational control in response to various stress conditions. Four eIF2α kinases, namely heme-regulated inhibitor (HRI), protein kinase R (PKR), PKR-like endoplasmic reticulum kinase, (PERK) and general control non-depressible 2 (GCN2), have been identified thus far, and they are known to be activated by heme depletion, viral infection, endoplasmic reticulum stress, and amino acid starvation, respectively. Because eIF2α is phosphorylated under various stress conditions, the existence of an additional eIF2α kinase has been suggested. To validate the existence of the unidentified eIF2α kinase, we constructed an eIF2α kinase quadruple knockout cells (4KO cells) in which the four known eIF2α kinase genes were deleted using the CRISPR/Cas9-mediated genome editing. Phosphorylation of eIF2α was completely abolished in the 4KO cells by various stress stimulations. Our data suggests that the four known eIF2α kinases are sufficient for ISR and that there are no additional eIF2α kinases in vertebrates.

    DOI: 10.1038/srep32886

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  • Functional characterization of the mouse melanocortin 3 receptor gene promoter. 査読 国際誌

    Keisuke Okutsu, Fumiya Ojima, Naoto Shinohara, Shusuke Taniuchi, Yasusyo Mizote, Kenji Aoki, Toshiyuki Kudo, Maho Ogoshi, Sakae Takeuchi, Sumio Takahashi

    Gene   562 ( 1 )   62 - 9   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Melanocortin receptor 3 (MC3R) is expressed in the hypothalamus and pituitary in humans and rodents, and is involved in the control of feeding, energy metabolism, and pituitary function. In the mouse pituitary, MC3R is detected in mammotrophs. This study aimed to clarify the regulatory mechanism for Mc3r expression in the mouse pituitary. The promoter activities of reporter constructs for the MC3R gene 5'-flanking region up to -4000 bp (transcription initiation site designated as +1) were analyzed. The promoter activity significantly increased in the -86/+109 construct, but decreased in the -38/+109 construct, indicating that the minimal promoter required for basal expression of Mc3r is located in the -86/+109 region. Putative binding sites for transcription factors AP-1 and ATF4 were found in the 5'-flanking region of Mc3r. Site-directed mutation or deletion of these sites affected the promoter activities. In gel-shift assays with a nuclear extract of mouse anterior pituitary cells, band-shifts were detected for both sites after the addition of the nuclear extract, and were decreased in the presence of excess unlabeled probe competitors. These results indicated that both sites were involved in the regulation of Mc3r expression in anterior pituitary cells. Estradiol-17β treatment increased the Mc3r promoter activity, indicating that the gene is regulated by estradiol-17β. In conclusion, we have demonstrated the minimum promoter region required for Mc3r expression, and identified two binding sites for AP-1 and ATF4 and in the 5' upstream-flanking region of Mc3r that are essential for Mc3r expression.

    DOI: 10.1016/j.gene.2015.02.043

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  • Production and characterization of neurosecretory protein GM using Escherichia coli and Chinese Hamster Ovary cells. 査読 国際誌

    Keiko Masuda, Megumi Furumitsu, Shusuke Taniuchi, Eiko Iwakoshi-Ukena, Kazuyoshi Ukena

    FEBS open bio   5   844 - 51   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM) are paralogs recently discovered in birds and in mammals. The post-translational products of NPGL and of NPGM genes include a signal peptide sequence, a glycine amidation signal, and a dibasic amino acid cleavage site. This suggests that the mature forms of NPGL and of NPGM are small proteins secreted in the hypothalamus and containing an amidated C-terminus. However, endogenous NPGL and NPGM have not yet been identified. Chicken NPGL and NPGM have two highly conserved Cys residues that are likely to form a disulfide bond, while mammalian NPGM has one additional Cys residue located between the two conserved Cys residues and the correct disulfide bond pattern is unclear. In this study, we prepared rat NPGM to elucidate the structure of its mature form. We first expressed the predicted mature NPGM, containing an extra C-terminal Gly, in Escherichia coli SHuffle cells, which are engineered to promote the formation of native disulfide bridges in recombinant proteins. We observed the presence of a disulfide bond between the N-terminal Cys residue and the second Cys residue, while the C-terminal Cys residue was free. Secondly, we transfected a construct containing the entire NPGM open reading frame into Chinese Hamster Ovary cells, and observed that NPGM was cleaved immediately after the signal peptide and that it was secreted into the medium. Furthermore, the protein presented a disulfide bond at the same location observed in recombinant NPGM.

    DOI: 10.1016/j.fob.2015.10.002

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  • Characterization of an avian histidine decarboxylase and localization of histaminergic neurons in the chicken brain. 査読 国際誌

    Yuki Bessho, Eiko Iwakoshi-Ukena, Tetsuya Tachibana, Sho Maejima, Shusuke Taniuchi, Keiko Masuda, Kenshiro Shikano, Kunihiro Kondo, Megumi Furumitsu, Kazuyoshi Ukena

    Neuroscience letters   578   106 - 10   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In mammals, it is established that histamine is a neurotransmitter and/or neuromodulator in the central nervous system. It is produced by the enzyme histidine decarboxylase (HDC) in the tuberomammillary nucleus of the posterior hypothalamus. However, HDC as well as histaminergic neurons have not yet been characterized in the avian brain. We have cloned the cDNA for HDC from the chicken hypothalamus and demonstrated that the chicken HDC sequence is highly homologous to the mammalian counterpart, and that the expressed protein shows high enzymatic activity. The expression of HDC mRNA at various sites in the brain was investigated using quantitative RT-PCR. The results showed that the HDC mRNA was highly expressed in the hypothalamic infundibulum. In situ hybridization analyses revealed that the cells containing HDC mRNA were localized in the medial mammillary nucleus of the hypothalamic infundibulum. Intracerebroventricular injection of histamine in chicks resulted in inhibition of feeding behavior. This is the first report of the characterization of histaminergic neurons in the avian brain, and our findings indicate that neuronal histamine exerts anorexigenic effects in chicks.

    DOI: 10.1016/j.neulet.2014.06.048

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  • Identification of neurotensin and LANT-6 and localization of mRNA encoding their precursor in the chicken brain. 査読

    Keiko Masuda, Eiko Iwakoshi-Ukena, Yuki Bessho, Shusuke Taniuchi, Sho Maejima, Kenshiro Shikano, Kunihiro Kondo, Megumi Furumitsu, Kazuyoshi Ukena

    Zoological science   31 ( 6 )   353 - 9   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Neurotensin (NT) and neurotensin-related peptide (Lys(8), Asn(9), NT(8-13): LANT-6) have previously been purified from chicken intestine. However, the presence of these peptides and the localization of their precursor mRNA in the brain were not well understood. In the present study, through a comprehensive analysis of bioactive substances, NT and LANT-6 were identified in the chicken brain using tandem mass spectrometry combined with a bioassay of the colon contraction. The effect of NT and LANT-6 on the colon contraction was assessed, and NT was found to be 10 times more potent than LANT-6. Furthermore, the sites of NT/LANT-6 precursor mRNA expression in the brain were investigated using quantitative RT-PCR. The result showed that the mRNA was expressed most in the telencephalon, followed by the diencephalon. In situ hybridization analysis revealed that cells containing NT/LANT-6 precursor mRNA were widely distributed throughout the brain except for the cerebellum. Additionally, these were highly concentrated in the frontal telencephalon, including the nidopallium, hyperpallium, and hippocampus. Collectively, these results indicate that NT and LANT-6 are produced in the chicken brain, and they may participate in multiple functions.

    DOI: 10.2108/zs140010

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  • Identification of a cDNA encoding a novel small secretory protein, neurosecretory protein GL, in the chicken hypothalamic infundibulum. 査読 国際誌

    Kazuyoshi Ukena, Eiko Iwakoshi-Ukena, Shusuke Taniuchi, Yuki Bessho, Sho Maejima, Keiko Masuda, Kenshiro Shikano, Kunihiro Kondo, Megumi Furumitsu, Tetsuya Tachibana

    Biochemical and biophysical research communications   446 ( 1 )   298 - 303   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To find novel neuropeptide and/or peptide hormone precursors in the avian brain, we performed a cDNA subtractive screen of the chicken hypothalamic infundibulum, which contains one of the feeding and neuroendocrine centers. After sequencing 596 clones, we identified a novel cDNA encoding a previously unknown protein. The deduced precursor protein consisted of 182 amino acid residues, including one putative small secretory protein of 80 amino acid residues. This small protein was flanked at the N-terminus by a signal peptide and at the C-terminus by a glycine amidation signal and a dibasic amino acid cleavage site. Because the predicted C-terminal amino acids of the small protein were Gly-Leu-NH2, the small protein was named neurosecretory protein GL (NPGL). Quantitative RT-PCR analysis demonstrated specific expression of the NPGL precursor mRNA in the hypothalamic infundibulum. Furthermore, the mRNA levels in the hypothalamic infundibulum increased during post-hatching development. In situ hybridization analysis showed that the cells containing the NPGL precursor mRNA were localized in the medial mammillary nucleus and infundibular nucleus within the hypothalamic infundibulum of 8- and 15-day-old chicks. Subcutaneous infusion of NPGL in chicks increased body weight gain without affecting food intake. To our knowledge, this is the first report to describe the identification and localization of the NPGL precursor mRNA and the function of its translated product in animals. Our findings indicate that NPGL may participate in the growth process in chicks.

    DOI: 10.1016/j.bbrc.2014.02.090

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  • IGF-1 gene expression is differentially regulated by estrogen receptors α and β in mouse endometrial stromal cells and ovarian granulosa cells. 査読

    Yuki Ogo, Shusuke Taniuchi, Fumiya Ojima, Sayo Hayashi, Itsuo Murakami, Yuka Saito, Sakae Takeuchi, Toshiyuki Kudo, Sumio Takahashi

    The Journal of reproduction and development   60 ( 3 )   216 - 23   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Insulin-like growth factor 1 (IGF-1) is involved in regulations of reproductive functions in rats and mice. IGF-1 expression is regulated by estrogen in several reproductive organs including the uterus and ovary. Two types of estrogen receptor (ERα and ERβ) are expressed in mouse uteri and ovaries, and it is unclear whether they differently mediate IGF-1 gene transcription. To clarify the roles of ERα and ERβ, mouse endometrial stromal cells and ovarian granulosa cells were treated with ligands specific for individual estrogen receptors. In endometrial stromal cells, propyl-pyrazole-triol (PPT; ERα-selective agonist) increased Igf1 mRNA expression, which was suppressed by methyl-piperidino-pyrazole (MPP, ERα-selective antagonist), while diarylpropionitrile (DPN, ERβ-potency selective agonist) increased Igf1 mRNA expression, which was inhibited by MPP but not by 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-α]pyrimidin-3-yl]phenol (PHTPP; ERβ antagonist). PHTPP enhanced the DPN-induced increase in Igf1 mRNA expression. In ovarian granulosa cells, E2 and DPN decreased Igf1 mRNA expression, whereas PPT did not affect Igf1 mRNA levels. In these cells, PHTPP inhibited the DPN-induced decrease in Igf1 mRNA expression. These results suggest that ERα facilitates Igf1 transcription, whereas ERβ appears to inhibit Igf1 gene transcription in mouse endometrial stromal cells and ovarian granulosa cells.

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  • Pit-1w may regulate prolactin gene expression in mouse testis. 査読 国際誌

    Kazuki Maeda, Shusuke Taniuchi, Sumio Takahashi, Sakae Takeuchi

    General and comparative endocrinology   178 ( 2 )   180 - 4   2012年9月

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    記述言語:英語  

    Pit-1 is a POU-domain transcription factor that promotes growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone β subunit (TSHβ) gene expression in the pituitary gland. Alternative splicing of Pit-1 gene transcripts has been shown to give rise to several variants with discrete transactivation properties. Recently, we identified a mouse Pit-1 w that is generated by alternative promoter usage and is expressed in a variety of tissues including the testis. Using a combination of reverse-transcription polymerase chain reaction analyses and luciferase reporter gene assays, we investigated the possible role of Pit-1 w in the mouse testis. In postnatal testicular development, the expression of Pit-1 w mRNA was significantly up-regulated between 18 and 20 days after birth when the numbers of secondary spermatocytes and spermatids have been reported to increase in mice. The PRL mRNA, but not the mRNAs for GH or TSHβ, showed intratesticular expression patterns that were similar to those of the Pit-1 w mRNA. In experimental unilaterally cryptorchid testes of adult mice, spermatid numbers were extremely low and the expression levels of both the Pit-1 w and PRL mRNAs dropped dramatically. Furthermore, in the luciferase reporter gene assays, we found that Pit-1 w specifically transactivated the PRL promoter but had no effect on the promoters of GH or TSHβ. These results suggested that Pit-1 w could be involved in the paracrine/autocrine system in mice and may be necessary for normal testicular function via its possible role in regulating PRL expression in testicular germ cells. This is the first report demonstrating the possible role of Pit-1 w in mammals.

    DOI: 10.1016/j.ygcen.2012.05.004

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  • Transforming growth factor-α mRNA expression and its possible roles in mouse endometrial stromal cells. 査読

    Tetsuya Maekawa, Atsuko Sakuma, Shusuke Taniuchi, Yuki Ogo, Taisen Iguchi, Sakae Takeuchi, Sumio Takahashi

    Zoological science   29 ( 6 )   377 - 83   2012年6月

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    記述言語:英語  

    Transforming growth factor-α (TGFα) is thought to be involved in the regulation of endometrial cells. We investigated Tgfa mRNA expression, and the effects of TGFα on DNA-synthesis and gene expression of insulin-like growth factor 1 (IGF1), IGF binding protein-3 (IGFBP3) and IGF1 receptor in the mouse endometrial cells, because IGF1 is involved in estrogen-induced growth of endometrial cells. We also investigated the role of TGFα on matrix metalloproteinase (MMP) expression, as MMPs are involved both in tissue remodeling during cell proliferation and in enhancement of IGF1 signaling through the degradation of IGFBP3. Tgfa mRNA expression was detected in endometrial luminal and glandular epithelial cells, and stromal cells. Tgfa mRNA signals did not appear to change in endometrial luminal epithelial cells, but signals in glandular epithelial cells were higher at diestrus 1, 2 and proestrus, and the number of stromal cells showing strong signals appeared to increase at diestrus 1 and 2. Endometrial epithelial and stromal cells were treated with estradiol-17β (E2) or progesterone (P4). E2 or P4 stimulated Tgfa mRNA expression in stromal cells. TGFα stimulated DNA synthesis in endometrial epithelial and stromal cells, while E2 and P4 stimulated DNA synthesis in stromal cells. In stromal cells, TGFα, at as low as 1 ng/ml, decreased Igfbp3 and Mmp9 mRNA levels, while high dose (10 ng/ml) of TGFα decreased Igf1 mRNA level and increased Mmp3 mRNA level. These results imply that TGFα stimulates proliferation of endometrial stromal cells through multiple mechanisms, including its regulation of Igfbp3 and Mmp3 transcription.

    DOI: 10.2108/zsj.29.377

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  • Elaborate color patterns of individual chicken feathers may be formed by the agouti signaling protein. 査読 国際誌

    Chihiro Yoshihara, Ayaka Fukao, Keita Ando, Yuichi Tashiro, Shusuke Taniuchi, Sumio Takahashi, Sakae Takeuchi

    General and comparative endocrinology   175 ( 3 )   495 - 9   2012年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hair and feather pigmentation is mainly determined by the distribution of two kinds of melanin, eumelanin and pheomelanin, which produce brown to black and yellow to red colorations, respectively. The agouti signaling protein (ASIP) acts as an antagonist or an inverse agonist of the melanocortin 1 receptor (MC1R), a G protein-coupled receptor for α-melanocyte-stimulating hormone (α-MSH). This antagonism of the MC1R by ASIP on melanocytes initiates a switch of melanin synthesis from eumelanogenesis to pheomelanogenesis in mammals. In the present study, we isolated multiple ASIP mRNA variants generated by alternative splicing and promoters in chicken feather follicles. The mRNA variants showed a discrete tissue distribution. However, mRNAs were expressed predominantly in the feather pulp of follicles. Paralleling mRNA distribution, ASIP immunoreactivity was observed in feather pulp. Interestingly, ASIP was stained with pheomelanin but not eumelanin in pulp areas that face developing barbs. We suggest that the elaborate color pattern of individual feathers is formed in part by the antagonistic action of ASIP that is produced by multiple mRNA variants in chicken feather follicles.

    DOI: 10.1016/j.ygcen.2011.12.009

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  • Runx3 expression and its roles in mouse endometrial cells. 査読

    Yukiko Tsuchiya, Yuka Saito, Shusuke Taniuchi, Atsuko Sakuma, Tetsuya Maekawa, Hiroshi Fukamachi, Sakae Takeuchi, Sumio Takahashi

    The Journal of reproduction and development   58 ( 5 )   592 - 8   2012年

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    記述言語:英語  

    Runx3 is a transcription factor that belongs to the Runx family. We studied the localization of Runx3 mRNA in the mouse uterus, and its function in the mouse endometrium using Runx3 knockout (Runx3(-/-)) mice. Runx3 mRNA was detected in the endometrial luminal epithelial cells, glandular epithelial cells and stromal cells below the epithelial cell layer on the luminal side. The uteri of Runx3(-/-) mice were smaller than those of wt mice. The endometrial layer and uterine glands of Runx3(-/-) mice were less developed than those of wild-type mice, and the endometrial stromal layer was thinner. Transforming growth factor β1 and β3 (TGFβ1 and β3) mRNA levels in endometrial stromal cells of Runx3(-/-) mice were low compared with those of wild-type mice. Estradiol-17β (E2) increased Tgfb2 mRNA levels in endometrial stromal cells of Runx3(-/-) mice, but not in those of wild-type mice. E2 increased epidermal growth factor (EGF) mRNA levels in endometrial stromal cells of wild-type mice, but did not increase those of Runx3(-/-) mice. The diminished Tgfb1 and Tgfb3 mRNA expressions may lead to the reduced proliferation of endometrial stromal cells. Alterations of E2-associated expressions of Tgfb2 and Egf mRNA in endometrial stromal cells of Runx3(-/-) mice may be associated with suppression of E2-dependent endometrial epithelial cell proliferation in Runx3(-/-) mice. Thus, Runx3 is likely to be a regulatory factor responsible for endometrial growth.

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  • Identification of mammalian Pit-1w, possibly involved in spermatogenesis in mice. 査読 国際誌

    Shusuke Taniuchi, Kazuki Maeda, Toshiyuki Kudo, Sumio Takahashi, Sakae Takeuchi

    General and comparative endocrinology   173 ( 2 )   289 - 94   2011年9月

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    記述言語:英語  

    Pit-1 is a pituitary-specific transcription factor responsible for pituitary development and hormone expression in mammals. Alternative splicing of Pit-1 gene transcripts has been shown to give rise to several variants with discrete transactivation properties; however, those arising from alternative promoters such as avian Pit-1 w have not yet been identified in mammals. Here, comparative genomics analysis followed by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of 5' cDNA ends (5'RACE) were used in identifying Pit-1 w mRNA in the mouse pituitary. The mouse Pit-1 w mRNA is generated by using an alternative promoter located in the first intron, as with chicken Pit-1 w, and is expressed in a wide variety of tissues besides the pituitary. In the testis, Pit-1 w is expressed as the predominant variant and a protein of 33 kDa. During the first wave of spermatogenesis, expression of Pit-1 w mRNA at substantial levels was observed from 3 weeks, but not at 1 or 2 weeks after birth. A combination of immunohistochemistry and in situ hybridization detected Pit-1 mRNA and Pit-1 immunoreactivity in the spermatogonia, spermatocytes, and spermatids in the testis of adult mice. Because secondary spermatocytes and haploid spermatids increase in number between 18 and 20 days after birth in mice, it is possible that mouse Pit-1 w plays a role in spermatogenesis. This is the first report demonstrating the expression of Pit-1 variants arising from alternative promoters in mammals.

    DOI: 10.1016/j.ygcen.2011.06.016

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  • Role of chicken Pit-1 isoforms in activating growth hormone gene. 査読 国際誌

    Daisuke Murase, Shusuke Taniuchi, Sakae Takeuchi, Hiromi Adachi, Norio Kansaku, Katsuichiro Okazaki, Takeshi Ohkubo

    General and comparative endocrinology   173 ( 2 )   248 - 52   2011年9月

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    記述言語:英語  

    In the present study, we expressed chicken (ch) Pit-1α (chPit-1α) and chPit-1γin vitro to compare the roles of chPit-1s in the transcription of the chicken growth hormone (chGH) gene. Both green fluorescence protein (GFP)-fused chPit-1γ and GFP-fused chPit-1α were localized in the nuclei of COS-7 cells. In a luciferase reporter gene assay, both chPit-1α and chPit-1γ transactivated the chGH promoter, and chPit-1α showed a more potent effect than chPit-1γ. On the other hand, an increase of cellular cAMP induced by forskolin promoted transactivation of the chGH gene with chPit-1α and chPit-1γ to similar extents. These results suggest that chPit-1γ may modulate the basal promoter activity of the chGH gene to the same degree as chPit-1α; however, a structural difference observed at the N-terminus transactivation domains in chPit-1α and chPit-1γ could be associated with the efficiency of basal activation of the chGH promoter.

    DOI: 10.1016/j.ygcen.2011.06.007

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  • Feather follicles express two classes of pro-opiomelanocortin (POMC) mRNA using alternative promoters in chickens. 査読 国際誌

    Chihiro Yoshihara, Yuichi Tashiro, Shusuke Taniuchi, Harumi Katayama, Sumio Takahashi, Sakae Takeuchi

    General and comparative endocrinology   171 ( 1 )   46 - 51   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Feather coloration in chickens mainly depends on melanin produced by melanocytes located in the feather follicles. The melanocortin 1 receptor (MC1R) on follicular melanocytes regulates melanin synthesis; however, the source of the melanocortins that interact with the receptors remains unclear. In this study, we examine the potential expression of melanocortins and characterize the mRNAs for the precursor pro-opiomelanocortin (POMC) in chicken feather follicles. Reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of mRNAs for POMC, prohormone convertase 1 (PC1) and PC2, and western blotting detected adrenocorticotropic hormone (ACTH)-related products of POMC processing in feather follicles, suggesting that melanocortins are produced locally in the tissues of chickens. A combination of 5'RACE (rapid amplification of cDNA 5' end), 3'RACE and RT-PCR analyzes identified two classes of POMC mRNA, class a and class b, which encode the same full-length POMC protein but have different non-coding leader exons. Class a mRNAs were expressed specifically in feather follicles, whereas class b mRNAs were expressed in the pituitary, hypothalamus, and various peripheral tissues that we examined. Within the feather follicles, the class a mRNAs were distributed in epidermal layers from middle to distal locations, whereas the class b mRNAs were mainly expressed in pulp at proximal locations. Our findings suggest that feather pigmentation is regulated by locally produced melanocortins, and indicate that the melanocortins encoded by the different classes of POMC mRNAs may play different intra-follicular roles in chickens. This is the first report that demonstrates alternative promoter usage generating different full-length POMC mRNAs in vertebrates.

    DOI: 10.1016/j.ygcen.2010.12.018

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  • Identification of unique thyrotropin receptor (TSHR) splice variants in the chicken: the chicken TSHR gene revisited. 査読 国際誌

    Sylvia V H Grommen, Shusuke Taniuchi, Veerle M Darras, Sumio Takahashi, Sakae Takeuchi, Bert De Groef

    General and comparative endocrinology   156 ( 3 )   460 - 3   2008年5月

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    記述言語:英語  

    We previously described the cloning of the full-length chicken thyrotropin receptor (TSHRa) and two splice variants, lacking exon 3 (TSHRb) or both exons 2 and 3 (TSHRc). Here we report the identification of three novel splice variants of the chicken TSHR, named TSHRd, -e and -f, differing in their C-terminal region and containing unique exonic sequences that are not present in the other TSHR variants. This finding suggests a TSHR gene structure with 13 rather than the previously assumed 10 exons. The three novel exons appear to be chicken-specific, as no equivalents of these exons were found in other vertebrate genomes. Like the full-length receptor, the five TSHR splice variants are most abundantly expressed in thyroid gland. TSHRb, -d, -e and -f mRNA was also present in virtually all extra-thyroidal tissues expressing TSHRa, whereas TSHRc shows a more restricted tissue distribution. Whether these receptor transcripts are translated to functional proteins needs to be verified, but if so, they could be attributed various physiological roles.

    DOI: 10.1016/j.ygcen.2008.03.003

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  • Molecular cloning, tissue distribution, and ontogenic thyroidal expression of the chicken thyrotropin receptor. 査読 国際誌

    Sylvia V H Grommen, Shusuke Taniuchi, Tom Janssen, Liliane Schoofs, Sumio Takahashi, Sakae Takeuchi, Veerle M Darras, Bert De Groef

    Endocrinology   147 ( 8 )   3943 - 51   2006年8月

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    記述言語:英語  

    TSH and the interaction with its receptor (TSHR) in the thyroid gland play a crucial role in the pituitary-thyroid axis of all vertebrates. Released upon stimulation by TSH, thyroid hormones influence numerous processes in the body and are extremely important during the last week of chicken embryonic development. In this study, we have cloned and functionally characterized the chicken TSHR (cTSHR), which was found to be a G protein-coupled receptor consisting of 10 exons. Besides the full-length cDNA, we detected two splice variants lacking either exon 3, or exons 2 and 3, both part of the extracellular domain of the receptor. Bovine TSH increased intracellular cAMP levels in HEK-239 cells transiently expressing the full-length cTSHR (EC50 = 1.43 nm). In situ hybridization showed the expression of cTSHR mRNA in the thyroidal follicular cells. cTSHR mRNA expression, as determined by real-time PCR, was also found in several other tissues such as brain, pituitary, pineal gland, and retina, suggesting that the TSH-TSHR interaction is not only important in regulating thyroid function. TSHR mRNA expression in the thyroid gland did not change significantly during the last week of embryonic development, which suggests that an increased thyroidal sensitivity is not part of the cause of the concomitant increasing T4 levels.

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MISC

  • Identification of a chemical chaperone for mitigating protein aggregation and proteotoxicity during endoplasmic reticulum stress 国際誌

    Keisuke Kitakaze, Shusuke Taniuchi, Eri Kawano, Yoshimasa Hamada, Masato Miyake, Miho Oyadomari, Hirotatsu Kojima, Hidetaka Kosako, Tomoko Kuribara, Suguru Yoshida, Takamitsu Hosoya, Seiichi Oyadomari

    The FASEB Journal   35 ( S1 )   2021年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

    DOI: 10.1096/fasebj.2021.35.S1.01505

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  • 新規視床下部分泌性小タンパク質(NPGM)はニワトリの体重増加を亢進させる

    鹿野健史朗, 谷内秀輔, 岩越(浮穴)栄子, 別所裕紀, 前嶋翔, 益田恵子, 近藤邦裕, 古満芽久美, 橘哲也, 浮穴和義

    日本動物学会中国四国支部会報   ( 66 )   2014年

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  • ニワトリにおいて視床下部漏斗部に特異的発現を示す新規遺伝子の同定

    岩越 栄子, 橘 哲也, 谷内 秀輔, 古満 芽久美, 益田 恵子, 浮穴 和義

    日本家禽学会誌   50 ( 1 )   J10 - J15   2013年4月

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    記述言語:日本語   出版者・発行元:日本万国家禽学会  

    我々は,ニワトリの摂食調節に関わる新規脳内因子を発見する目的で,cDNAサブトラクション法を用いて,摂食調節中枢の一つである漏斗核を含む視床下部漏斗部に高発現する遺伝子を探索した。その結果,神経ペプチドの前駆体タンパク質をコードしていると推定される遺伝子の部分配列を見出した。その塩基配列は,機能未知のタンパク質をコードする遺伝子としてニワトリのゲノムデータベースに登録されている配列と一致した。そこでニワトリ品種間での多型の存在を明らかにするために,卵用鶏と肉用鶏の脳組織から,本遺伝子の翻訳領域の全長をコードするcDNAを単離し,ゲノムデータベース上のcDNA配列と比較した。その結果,卵用鶏では1アミノ酸残基の置換に相当する非同義置換が認められた。その塩基配列から推定されるアミノ酸配列から,前駆体タンパク質は,シグナル配列,神経ペプチド,C末端アミド化シグナル,プロセッシング配列,および,C末端付加配列の構造を有することが推定された。次に,脳内での本遺伝子のmRNA発現分布を解析したところ,視床下部漏斗部にのみ特異的に発現していることが明らかになった。初生ヒナでの視床下部漏斗部におけるmRNA発現量は,卵用鶏での発現量が肉用鶏に比べ約6倍多かった。さらに,推定される83アミノ酸残基からなる神経ペプチドを大腸菌の組換えタンパク質発現系を利用して産出し,その脳室内投与がニワトリヒナの摂食行動に及ぼす影響を調べた。その結果,本神経ペプチドは卵用鶏の摂食行動を抑制するが,肉用鶏の摂食行動には有意な影響を及ぼさないことが明らかになった。本研究から,新規遺伝子の翻訳産物と推定される神経ペプチドは,家禽の摂食行動を調節する新たな脳内因子である可能性が示された。

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    その他リンク: https://agriknowledge.affrc.go.jp/RN/2010851404

  • ニワトリで発見した新規神経ペプチドはヒスタミンニューロンに発現している

    別所裕紀, 岩越(浮穴)栄子, 古満芽久美, 前嶋翔, 谷内秀輔, 橘哲也, 浮穴和義

    日本動物学会中国四国支部会報   ( 65 )   2013年

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  • ニワトリの視床下部で見つけた神経ペプチドが摂食行動と成長に与える影響

    谷内秀輔, 岩越(浮穴)栄子, 別所裕紀, 古満芽久美, 橘哲也, 浮穴和義

    Annual Meeting of Japanese Avian Endocrinology   37th   2013年

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  • ニワトリで発見した神経ペプチド産生細胞の形態学的解析

    別所裕紀, 岩越(浮穴)栄子, 谷内秀輔, 前嶋翔, 古満芽久美, 橘哲也, 浮穴和義

    Annual Meeting of Japanese Avian Endocrinology   37th   2013年

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  • ニワトリ視床下部で発見した新規遺伝子がコードしている神経ペプチドの機能解析

    谷内秀輔, 岩越(浮穴)栄子, 古満芽久美, 橘哲也, 浮穴和義

    日本動物学会大会予稿集   83rd   2012年

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  • 鳥類ニワトリの視床下部で発見した新規神経ペプチドの前駆体遺伝子の解析

    浮穴和義, 浮穴(岩越)栄子, 谷内秀輔, 古満芽久美, 橘哲也

    日本動物学会中国四国支部会報   ( 64 )   2012年

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  • 転写因子Pit-1の下垂体外組織における発現と下垂体ホルモンの発現制御

    谷内 秀輔, 高橋 純夫, 竹内 栄

    岡山実験動物研究会報   27 ( 27 )   31 - 35   2011年5月

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    記述言語:日本語   出版者・発行元:岡山実験動物研究会  

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  • 日本下垂体研究会第26回学術集会印象記

    谷内 秀輔

    比較内分泌学   37 ( 143 )   247 - 248   2011年

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    記述言語:日本語   出版者・発行元:日本比較内分泌学会  

    DOI: 10.5983/nl2008jsce.37.247

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  • Transforming growth factor-alpha regulates insulin-like growth factor binding protein-3 gene expression in the mouse endometrial stromal cells

    Sumio Takahashi, Tetsuya Maekawa, Atsuko Sakuma, Shusuke Taniuchi, Munetoshi Kanayama, Taisen Iguchi, Sakae Takeuchi

    ENDOCRINE JOURNAL   57   S594 - S594   2010年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPAN ENDOCRINE SOC  

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受賞

  • 第16回日本臨床ストレス応答学会若手研究奨励賞

    2022年11月   日本臨床ストレス応答学会   小胞体ストレスセンサーPERKの活性化によるリン酸化を介したHMGB1の分泌機構

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  • 第13回若手研究奨励賞

    2013年10月   日本神経内分泌学会   視床下部で見つけた新規神経ペプチド前駆体遺伝子のラットの成長と脂肪蓄積に対する影響

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  • 優秀発表賞

    2013年8月   日本下垂体研究会   視床下部で発見した新規神経ペプチド前駆体遺伝子の機能解析

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  • 岡山大学理学部長賞

    2007年3月   岡山大学  

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共同研究・競争的資金等の研究課題

  • 小胞体ストレスセンサーPERKの活性化によるリン酸化を介したHMGB1の分泌機構

    研究課題/領域番号:20K07359  2020年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    谷内 秀輔

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    配分額:4,290,000円 ( 直接経費:3,300,000円 、 間接経費:990,000円 )

    前年度に同定したHMGB1の非リン酸化ミミック変異体と強く結合することが示された3種類のタンパク質が、LPS投与時のHMGB1分泌量に影響を及ぼすか否かを検証するため、本年度はCRISPR/Cas9システムを用いてRAW264.7細胞において当該遺伝子の破壊を試みた。
    3種類の遺伝子のうち、1種類の遺伝子についてはゲノム編集効率が比較的高い細胞プールが得られたため、細胞のクローン化を試みた。クローン化した細胞のゲノムDNAのシークエンス解析を行ったが、フレームシフト変異が全てのアリルに導入された完全なノックアウト細胞は得られなかった。しかし、ウエスタンブロット法で解析を行ったところ、標的遺伝子のタンパク質発現が野生型の細胞と比較して60~70%減少していた。完全なノックアウト細胞が得られなかった理由としては、当該遺伝子が細胞の生存に必須であるためと推察された。興味深いことに、ゲノム編集の標的遺伝子のタンパク質発現が減少していた細胞では、HMGB1の非リン酸化ミミック変異体と結合することが示された他のタンパク質の発現も減少させていた。
    現在、樹立したクローン細胞を用いてLPS投与時のHMGB1の分泌に対する当該遺伝子の影響の解析を進めている。また、データベースを用いた解析から、HMGB2もHMGB1と同様に前年度に同定した3種類のタンパク質と相互作用することが明らかになっているため、HMGB2の分泌についても解析を進めている。

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  • 視床下部で発現する新規神経ペプチド前駆体遺伝子が成長と脂肪蓄積に与える影響の解析

    2013年

    公益財団法人 内藤記念科学振興財団  2013年度 内藤記念特定研究助成金 

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    担当区分:研究代表者 

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  • 転写因子Pit-1による下垂体ホルモンの組織特異的発現制御機構の解明

    研究課題/領域番号:09J05209  2009年 - 2010年

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    谷内 秀輔

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    配分額:1,400,000円 ( 直接経費:1,400,000円 )

    Pit-1wの転写活性化能を明らかにするため,マウスPit-1w発現ベクターを作製し,成長ホルモン(GH),プロラクチン(PRL),甲状腺刺激ホルモンβサブユニット(TSHβ)遺伝子のプロモーターの転写活性に与える影響をHEK293細胞においてレポーター解析により調べた。その結果,Pit-1wはPRLのプロモーターの転写活性を有意に増加させたが,その増加率はPit-1αと比較して低かった。一方,Pit-1wはGHおよびTSHβのプロモーターの転写活性を増加させなかった。これらの結果は,ニワトリPit-1w発現ベクターを用いたレポーター解析の結果と一致しており,Pit-1wの機能は鳥類と哺乳類の間で共通であると考えられた。
    精巣におけるPit-1wの生理的機能を明らかにするため,1,2,3,4,5,6,8,10週齢のICR系統マウスの精巣においてGH,PRL,TSHβのmRNA発現とPit-1wのmRNAおよびタンパク発現との相関を調べた。GHおよびTSHβの発現はPit-1wの発現パターンとの相関が見られなかった。PRLの発現は1,2週齢では低く,3週齢以降に急上昇するというPit-1wと同様の発現パターンを示した。Pit-1mRNA発現細胞を同定するために,8週齢のICR系統マウスの精巣においてin situ hybridization法を行ったところ,一部の精原細胞および全ての精母細胞,精子細胞において陽性シグナルが検出され,特に精母細胞で強い陽性シグナルが得られた。精母細胞および精子細胞は2週齢から3週齢の間に増加することが知られており,その時期はPit-1w mRNAの発現が急上昇する時期と一致する。以上のことから,マウスの精巣においてPit-1wはPRLの発現を制御するとともに精母細胞への分化以降の精子形成に関与する可能性が示唆された。

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担当経験のある科目(授業)

  • 医学チュートリアルI

    2023年 - 現在 機関名:旭川医科大学

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  • 医学研究特論

    2021年 - 現在 機関名:旭川医科大学

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  • 薬理学実習

    2021年 - 現在 機関名:旭川医科大学

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