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農学部 獣医学科 |
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Matsuda K, Watanabe K, Miyagawa Y, Maruyama K, Konno N, Nakamachi T
Peptides 156 170846 - 170846 2022年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Peptides
Neuromedin U (NMU) is a multifunctional neuropeptide implicated in regulation of smooth muscle contraction in the circulatory and digestive systems, energy homeostasis and the stress response, but especially food intake in vertebrates. Recent studies have indicated the possible involvement of NMU in the regulation of psychomotor activity in rodents. We have identified four cDNAs encoding three putative NMU variants (NMU-21, −25 and −38) from the goldfish brain and intestine. Recently, we have also purified these NMUs and the truncated C-terminal form NMU-9 from these tissues, and demonstrated their anorexigenic action in goldfish. However, there is no information on the brain localization of NMU-like immunoreactivity and the psychophysiological roles of NMU in fish. Here, we investigated the brain distribution of NMU-like immunoreactivity and found that it was localized throughout the fore- and mid-brains. We subsequently examined the effect of intracerebroventricular (ICV) administration of NMU-21, which is abundant only in the brain on psychomotor activity in goldfish. As goldfish prefer the lower to the upper area of a tank, we developed an upper/lower area preference test in a tank for evaluating the psychomotor activity of goldfish using a personal tablet device without an automatic behavior-tracking device. ICV administration of NMU-21 at 10 pmol g-1 body weight (BW) prolonged the time spent in the upper area of the tank, and this action mimicked that of ICV administration of the central-type benzodiazepine receptor (CBR) agonist tofisopam at 100 pmol g-1 BW. These results suggest that NMU-21 potently induces anxiolytic-like action in the goldfish brain.
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Tanaka Y., Taguchi S., Maruyama K., Mori K., Miyazato M., Kangawa K., Murakami N., Nakahara K.
Biochemical and Biophysical Research Communications 534 653 - 658 2021年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biochemical and Biophysical Research Communications
© 2020 Elsevier Inc. Two novel peptides, neuromedin U precursor-related peptide (NURP) and neuromedin S precursor-related peptide (NSRP), are produced from neuromedin U (NMU) and neuromedin S (NMS) precursors, respectively, as these precursors have multiple consensus sequences for proteolytic processing. Our group has shown previously that one of these two novel peptides, NURP, stimulates body temperature and locomotor activity, but not food intake. However, the physiological function of the other peptide, NSRP, has remained unclear. Therefore, the aim of this study was to characterize differences in the regions of the rat brain targeted by the NMU/NMS peptide family, including NURP and NSRP, and their physiological functions. First, we explored the regions of c-Fos expression after intracerebroventricular (i.c.v.) injection of NURP and NSRP and found that these were fewer than after i.c.v. injection of NMU and NMS in the hypothalamus, possibly because NURP and NSRP cannot activate NMU/NMS receptors. In the ventral subiculum, which is one region of the hippocampus, c-Fos expression was evident only after i.c.v. injection of NURP. We also examined the effects of NSRP on food intake, body temperature and locomotor activity. Like NURP, NSRP increased both body temperature and locomotor activity, but not food intake, indicating that NSRP is also a functional peptide. However, these effects of NSRP were distinctly weaker than those of NURP. These findings suggest differences in the affinity of NURP and/or NSRP for specific receptors, or in their respective biological activities.
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Neuromedin U suppresses prolactin secretion via dopamine neurons of the arcuate nucleus 査読あり
Nakahara K., Maruyama K., Ensho T., Mori K., Miyazato M., Kangawa K., Uemura R., Sakoda H., Nakazato M., Murakami N.
Biochemical and Biophysical Research Communications 521 ( 2 ) 521 - 526 2020年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biochemical and Biophysical Research Communications
© 2019 Neuromedin U (NMU) has a precursor that contains one additional peptide consisting of 33 or 36 amino acid residues. Recently, we identified this second peptide from rat brain and designated it neuromedin U precursor-related peptide (NURP), showing it to stimulate prolactin release from the pituitary when injected via the intracerebroventricular (icv) route. Here, we examined whether NMU, like NURP, also stimulates prolactin release. Unlike NURP, icv injection of NMU significantly decreased the secretion of prolactin from the pituitary. This suppression of prolactin release by NMU was observed in hyper-prolactin states such as lactation, stress, pseudopregnancy, domperidone (dopamine antagonist) administration, and icv injection of NURP. Immunohistochemical analysis revealed that icv injection of NMU induced cFos expression in dopaminergic neurons of the arcuate nucleus, but not the substantia nigra. Mice with double knockout of NMU and neuromedin S (NMS), the latter also binding to NMU receptors, showed a significant increase of the plasma prolactin level after domperidone treatment relative to wild-type mice. These results suggest that NMU and NURP may play important reciprocal roles in physiological prolactin secretion.
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Liver-expressed antimicrobial peptide 2 antagonizes the effect of ghrelin in rodents 査読あり
Islam M., Mita Y., Maruyama K., Tanida R., Zhang W., Sakoda H., Nakazato M.
The Journal of endocrinology 244 ( 1 ) 13 - 23 2020年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：The Journal of endocrinology
Ghrelin, a stomach-derived peptide, promotes feeding and growth hormone (GH) secretion. A recent study identified liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous inhibitor of ghrelin-induced GH secretion, but the effect of LEAP2 in the brain remained unknown. In this study, we showed that intracerebroventricular (i.c.v.) administration of LEAP2 to rats suppressed central ghrelin functions including Fos expression in the hypothalamic nuclei, promotion of food intake, blood glucose elevation, and body temperature reduction. LEAP2 did not inhibit neuropeptide Y (NPY)-induced food intake or des-acyl ghrelin-induced reduction in body temperature, indicating that the inhibitory effects of LEAP2 were specific for GHSR. Plasma LEAP2 levels varied according to feeding status and seemed to be dependent on the hepatic Leap2 expression. Furthermore, ghrelin suppressed the expression of hepatic Leap2 via AMPK activation. Together, these results reveal that LEAP2 inhibits central ghrelin functions and crosstalk between liver and stomach.
DOI： 10.1530/JOE-19-0102
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Purification and identification of native forms of goldfish neuromedin U from brain and gut 査読あり
Maruyama K., Kaiya H., Miyazato M., Murakami N., Nakahara K., Matsuda K.
Biochemical and Biophysical Research Communications 517 ( 3 ) 433 - 438 2019年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biochemical and Biophysical Research Communications
© 2019 Neuromedin U (NMU) plays important roles in energy homeostasis in rodents and birds. Previously, our group has isolated four cDNAs encoding precursor proteins of NMU from the goldfish brain and gut, and it was assumed that these transcripts are produced by alternative splicing. We have also demonstrated that intracerebroventricular (ICV) injection of putative goldfish NMU inhibits food intake. However, as native goldfish NMU has not yet been identified, we attempted to purify it from goldfish brain and gut extracts. To assess NMU activity in fractions at each purification step, we measured changes in the intracellular concentrations of Ca2+ using HEK293 cells expressing goldfish NMU-R1 or -R2. We isolated a 25-amino-acid peptide (NMU-25) from the brain and gut and found that its primary structure is similar to that of mammalian NMU. Another 21-amino-acid peptide (NMU-21) was purified from the brain, but not from the gut. Furthermore, a 9-amino-acid peptide (NMU-9) identical to the C-terminus of NMU-21 and -25 was also isolated from the brain and gut. Treatment with synthetic NMU-9, -21 and -25 dose-dependently increased the intracellular Ca2+ concentration in mammalian cells expressing goldfish NMU-R1 and -R2. We also examined the effect of ICV-administered synthetic goldfish NMUs on goldfish food intake. NMU-25 inhibited food intake to the same degree as NMU-21. However, the inhibitory effect of NMU-9 was slightly weaker than those of NMU-21 and -25. These results indicate that several molecular forms of NMU exist in the goldfish brain and gut, and that all of them play physiological roles via NMU-R1 and NMU-R2.
講演・口頭発表等 【 表示 ／ 非表示 】
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ニューロメジンS前駆体中の新規ペプチド（NSRP）の生理機能の探索
田口 史門、延生 卓也、森 健二、宮里 幹也、寒川 賢治、丸山 圭介、村上 昇、中原 桂子
第162回日本獣医学会学術集会 (茨城県つくば市 つくば国際会議場) 日本獣医学会
開催年月日： 2019年9月10日 - 2019年9月12日
記述言語：日本語 会議種別：口頭発表（一般）
開催地：茨城県つくば市 つくば国際会議場
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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スプライシングバリアントの探索を基盤とした、NURPとNMUの生理的役割の解明
研究課題/領域番号：22K06045 2022年04月 - 2025年03月
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
担当区分：研究代表者
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摂食・エネルギー代謝を制御する新規生理活性ペプチドの発見と応用
研究課題/領域番号：21K05958 2021年04月 - 2024年03月
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
担当区分：研究分担者
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新規ペプチド"NURP"と"NSRP"のトランスレーショナルリサーチ
研究課題/領域番号： 20H03153 2020年04月 - 2024年03月
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
中原 桂子、
担当区分：研究分担者
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NMUとの機能的連関に着目した、新規ペプチドホルモンNURPの生理機能の解明
研究課題/領域番号：19K09009 2019年 - 2022年03月
科学研究費補助金 基盤研究(C)
担当区分：研究代表者
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肥満減量手術モデルラットの消化管から分泌される機能性タンパク質の生理機能の解明
研究課題/領域番号： 16K19553 2016年04月 - 2019年03月
科学研究費補助金 若手研究(B)