Identification and functional analysis of novel bioactive peptides associated with feeding regulation and lifestyle-related disease

• Project/Area Number: 21591189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: MIYAZATO Mikiya 独立行政法人国立循環器病研究センター, 生化学部, 部長 (50291183)
• Co-Investigator(Renkei-kenkyūsha): KANGAWA Kenji 独立行政法人国立循環器病研究センター, 研究所, 所長 (00112417) ; DATE Yukari 宮崎大学, フロンティア科学実験総合センター, 教授 (70381100)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ペプチド / 摂食調節 / 生活習慣病 / オーファン受容体

Research Abstract

To search for novel bioactive peptides associated with feeding regulation and lifestyle-related diseases, we used the orphan receptor strategy and newly established methods to find some candidates as novel bioactive substances. By using gene deficient mice of ghrelin or neuromed in S(NMS), we demonstrated that endogenous ghrelin suppresses sympathetic nerve activity and improves the prognosis after acute myocardial infarction, and that endogenous NMS may regulate cardiovascular function by activating the sympathetic nervous system.

Research Products

• [Journal Article] Ghrelin Prevents Incidence of Malignant Arrhythmia after Acute Myocardial Infarction through Vagal Afferent Nerves (2012)
  • Author(s): Mao Y, Tokudome T, Otani K, Kishimoto I, Nakanishi M, Hosoda H, Miyazato M, Kangawa K
  • Journal Title: Endocrinology Volume: (in press) Issue: 7 Pages: 3426-3434
  • DOI: 10.1210/en.2012-1065
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein-3b(BMP-3b) is expressed in adipocytes and inhibits adipogenesis as a unique complex (2012)
  • Author(s): Hino J, Miyazawa T, Miyazato M, Kangawa K
  • Journal Title: Int J Obes Volume: 36 Issue: 5 Pages: 725-734
  • DOI: 10.1038/ijo.2011.124
  • Peer Reviewed
• [Journal Article] Ghrelin and cardiovascular diseases (2012)
  • Author(s): Kishimoto I, Tokudome T, Hosoda H, Miyazato M, Kangawa K
  • Journal Title: J Cardiology Volume: 59 Issue: 1 Pages: 8-13
  • DOI: 10.1016/j.jjcc.2011.11.002
  • NAID: 10019807283
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein-3b(BMP-3b) inhibits osteoblast differentiation via Smad2/3 pathway by counteracting Smad1/5/8 signaling (2012)
  • Author(s): Matsumoto Y, Otsuka F, Hino J, Miyoshi T, Takano M, Miyazato M, Makino H, Kangawa
  • Journal Title: Mol Cell Endocrinol Volume: 350 Issue: 1 Pages: 78-86
  • DOI: 10.1016/j.mce.2011.11.023
  • Peer Reviewed
• [Journal Article] Identification of the endogenous cysteine-rich peptide trissin, ligand for an orphan G-protein-coupled receptor in Drosophila (2011)
  • Author(s): Ida T, Takahashi T, Tominaga H, Sato T, Kume K, Yoshizawa-Kumagae K, Nishio H, Kato J, Murakami N, Miyazato M, Kangawa K, Kojima M
  • Journal Title: Biochem Biophys Res Commun Volume: 414 Issue: 1 Pages: 44-48
  • DOI: 10.1016/j.bbrc.2011.09.018
  • Peer Reviewed
• [Journal Article] Two chicken neuromedin U receptors : Characterization of primary structure, biological activity and tissue distribution (2011)
  • Author(s): Yamamoto I, Nakao N, Kaiya H, Miyazato M, Tsushima N, Arai T, Tanaka M
  • Journal Title: General and Comparative Endocrinology Volume: 174 Issue: 2 Pages: 116-123
  • DOI: 10.1016/j.ygcen.2011.08.004
  • Peer Reviewed
• [Journal Article] Ghrelin receptor in two species of anuran amphibian, bullfrog(Rana catesbeiana) and Japanese tree frog(Hyla japonica) (2011)
  • Author(s): Kaiya H, Koizumi Y, Konno N, Yamamoto K, Uchiyama M, Kangawa K, Miyazato M
  • Journal Title: Front Exp Endocrinol Volume: 2 Pages: 1-13
  • DOI: 10.3389/fendo.2011.00031
  • Peer Reviewed
• [Journal Article] Identification of the novel bioactive peptides dRYamide-1 and dRYamide-2, ligands for a neuropeptide Y-like receptor in Drosophila (2011)
  • Author(s): Ida T, Takahashi T, Tominaga H, Sato T, Kume K, Ozak Mi, Hiraguchi T, Maeda T, Shiotani H, Terajima S, Sano H, Mori K, Yoshida M, Miyazato M, Kato J, Murakami N, Kangawa K, Kojima M
  • Journal Title: Biochem Biophys Res Commun Volume: 410 Issue: 4 Pages: 872-877
  • DOI: 10.1016/j.bbrc.2011.06.081
  • Peer Reviewed
• [Journal Article] Recent advances in the phylogenetic study of ghrelin (2011)
  • Author(s): Kaiya H, Miyazato M, Kangawa K
  • Journal Title: Peptides Volume: 32 Issue: 11 Pages: 2155-2174
  • DOI: 10.1016/j.peptides.2011.04.027
  • Peer Reviewed
• [Journal Article] A Guanosine 3', 5'-cyclic monophosphate(cGMP) reporter system based on the G-Kinase/CREB/CRE signal transduction pathway (2011)
  • Author(s): Okano I, Miyazato M, Kangawa K
  • Journal Title: Biochem Biophys Res Commun Volume: 407 Issue: 1 Pages: 236-241
  • DOI: 10.1016/j.bbrc.2011.03.009
  • Peer Reviewed
• [Journal Article] Neuromedin S regulates cardiovascular function through the sympathetic nervous system in mice (2011)
  • Author(s): Sakamoto T, Nakahara K, Maruyama K, Katayama T, Mori K, Miyazato M, Kangawa K, Murakami N
  • Journal Title: Peptides Volume: 32 Issue: 5 Pages: 1020-1026
  • DOI: 10.1016/j.peptides.2011.02.015
  • Peer Reviewed
• [Journal Article] Isolation and characterization of two cDNAs encoding the neuromedin U receptor from goldfish brain (2011)
  • Author(s): Maruyama K, Kaiya H, Miyazato M, Konno N, Wakasugi T, Uchiyama M, Shioda S, Murakami N, Matsuda K
  • Journal Title: J Neuroendocrinol Volume: 23 Issue: 3 Pages: 282-291
  • DOI: 10.1111/j.1365-2826.2010.02106.x
  • Peer Reviewed
• [Journal Article] Guanosine 3',5'-cyclic monophosphate (cGMP) reporter system based on the G-Kinase/CREB/CRE signal transduction pathway. (2011)
  • Author(s): Okano I, et al.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 407 Pages: 236-241
  • Peer Reviewed
• [Journal Article] Neuromedin S regulates cardiovascular function through the sympathetic nervous system inmice. (2011)
  • Author(s): Sakamoto T, et al.
  • Journal Title: Peptides Volume: 32 Pages: 1020-1026
  • Peer Reviewed
• [Journal Article] Molecular characterization of structure and tissue distribution of chicken neurotensin receptor. (2011)
  • Author(s): Numano M, et al.
  • Journal Title: Gen.Comp.Endocrinol. Volume: 171 Pages: 33-38
  • Peer Reviewed
• [Journal Article] Isolation and characterization of two cDNAs encoding the neuromedin U receptor from goldfish brain. (2011)
  • Author(s): Maruyama K, et al.
  • Journal Title: J.Neuroendocrinol. Volume: 23 Pages: 282-291
  • Peer Reviewed
• [Journal Article] Comparison of feeding suppression by the anorexigenic hormones neuromedin U and neuromedin S in rats (2010)
  • Author(s): Nakahara K, Katayama T, Maruyama K, Ida T, Mori K, Miyazato M, Kangawa K, Murakami N
  • Journal Title: J Endocrinol Volume: 207 Issue: 2 Pages: 185-193
  • DOI: 10.1677/joe-10-0081
  • Peer Reviewed
• [Journal Article] Nutritional and environmental factors affecting plasma ghrelin and leptin levels S in rats (2010)
  • Author(s): Nakahara K, Okame R, Katayama T, Miyazato M, Kangawa K, Murakami N
  • Journal Title: J Endocrinol Volume: 207 Issue: 1 Pages: 95-103
  • DOI: 10.1677/joe-10-0062
  • Peer Reviewed
• [Journal Article] Two functional growth hormone secretagogue receptor(ghrelin receptor) type 1a and 2a in goldfish, Carassius auratus (2010)
  • Author(s): Kaiya H, Miura T, Matsuda K, Miyazato M, Kangawa K
  • Journal Title: Mol Cell Endocrinol Volume: 327 Issue: 1-2 Pages: 25-39
  • DOI: 10.1016/j.mce.2010.06.004
  • Peer Reviewed
• [Journal Article] Neuromedin U is necessary for normal gastrointestinal motility and is regulated by serotonin (2010)
  • Author(s): Nakashima Y, Ida T, Sato T, Nakamura Y, Takahashi T, Mori K, Miyazato M, Kangawa K, Kusukawa J, Kojima M
  • Journal Title: Ann N Y Acad Sci Volume: 1200 Issue: 1 Pages: 104-111
  • DOI: 10.1111/j.1749-6632.2010.05504.x
  • Peer Reviewed
• [Journal Article] Purification and characterization of caprine ghrelin and its effect on growth hormone release (2010)
  • Author(s): Ida T, Miyazato M, Lin XZ, Kaiya H, Sato T, Nakahara K, Murakami N, Kangawa K, Kojima M
  • Journal Title: J Mol Neurosci Volume: 42 Issue: 1 Pages: 99-105
  • DOI: 10.1007/s12031-010-9379-0
  • Peer Reviewed
• [Journal Article] Comparison of feeding suppression by the anorexigenic hormones neuromedin U and neuromedin S in rats. (2010)
  • Author(s): Nakahara K, et al.
  • Journal Title: J.Endocrinol. Volume: 207 Pages: 185-193
  • Peer Reviewed
• [Journal Article] Nutritional and environmental factors affecting plasma ghrelin and leptin levels in rats (2010)
  • Author(s): Nakahara K, et al.
  • Journal Title: J.Endocrinol. Volume: 207 Pages: 95-103
  • Peer Reviewed
• [Journal Article] Two functional growth hormone secretagogue receptor (ghrelin receptor) type 1a and 2a in goldfish, Carassius auratus. (2010)
  • Author(s): Kaiya H, et al.
  • Journal Title: Mol.Cell.Endocrinol. Volume: 327 Pages: 25-39
  • Peer Reviewed
• [Journal Article] Neuromedin U is necessary for normal gastrointestinal motility and is regulated by serotonin. (2010)
  • Author(s): Nakashima Y, et al.
  • Journal Title: Ann.N.Y.Acad.Sci. Volume: 1200 Pages: 104-111
  • Peer Reviewed
• [Journal Article] Molecular cloning and characterization of V2-type receptor in two ray-finned fish, gray bichir, Polypterus senegalus and medaka, Oryzias latipes. (2010)
  • Author(s): Konno N, et al.
  • Journal Title: Peptides Volume: 31 Pages: 1273-1279
  • Peer Reviewed
• [Journal Article] Purification and characterization of caprine ghrelin and its effect on growth hormone release. (2010)
  • Author(s): Ida T, et al.
  • Journal Title: J.Mol.Neurosci. Volume: 42 Pages: 99-105
  • Peer Reviewed
• [Journal Article] Ghrelin-like peptide with fatty acid modification and O-glycosylation in the red stingray, Dasyatis akajei (2009)
  • Author(s): Kaiya, H., Kodama, S., Ishiguro, K., Matsuda, K., Uchiyama, M., Miyazato, M., and Kangawa, K.
  • Journal Title: BMC Biochem Volume: 10 Issue: 1 Pages: 30-30
  • DOI: 10.1186/1471-2091-10-30
  • Peer Reviewed
• [Journal Article] Impaired recovery of blood flow after hind-limb ischemia in mice lacking guanylyl cyclase-a, a receptor for atrial and brain natriuretic peptides (2009)
  • Author(s): Tokudome T, Kishimoto I, Yamahara K, Osaki T, Minamino N, Horio T, Sawai K, Kawano Y, Miyazato M, Sata M, Kohno M, Nakao K, Kangawa K
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 29 Issue: 10 Pages: 1516
  • DOI: 10.1161/atvbaha.109.187526
  • Peer Reviewed
• [Journal Article] Ghrelin receptor(GHS-R)-like receptor and its genomic organisation in rainbow trout, Oncorhynchus mykiss (2009)
  • Author(s): Kaiya H, Mori T, Miyazato M, Kangawa K
  • Journal Title: Comp Biochem Physiol A Mol Integr Physiol Volume: 153 Issue: 4 Pages: 438-450
  • DOI: 10.1016/j.cbpa.2009.04.612
  • Peer Reviewed
• [Journal Article] Identification and Genomic Sequence of Ghrelin Receptor(GHS-R)-like Receptor in the Mozambique Tilapia, Oreochromis mossambicus (2009)
  • Author(s): Kaiya H, Riley L, Janzen W, Hirano T, Grau EG, Miyazato M, Kangawa K
  • Journal Title: Zoolog Sci Volume: 26 Issue: 5 Pages: 330-337
  • DOI: 10.2108/zsj.26.330
  • NAID: 40016725993
  • Peer Reviewed
• [Journal Article] Ghrelin-like peptide with fatty acid modification and O-glycosylation in the red stingray, Dasyatis akajei. (2009)
  • Author(s): Hiroyuki Kaiya, et al.
  • Journal Title: BMC Biochem. 10 Pages: 30-30
  • Peer Reviewed
• [Journal Article] Impaired recovery of blood flow following hind-limb ischemia in micelacking guanylyl cyclase-A, a receptor for atrial and brain natriuretic peptides. (2009)
  • Author(s): Takeshi Tokudome, et al.
  • Journal Title: Arterioscler. Thromb. Vasc.Biol. 29 Pages: 1516-1521
  • Peer Reviewed
• [Journal Article] Ghrelin receptor(GHS-R)-like receptor and its genomic organisation in rainbow trout, Oncorhynchus mykiss. (2009)
  • Author(s): Hiroyuki Kaiya, et al.
  • Journal Title: Comp.Biochem. Physiol. A Mol.Integr. Physiol. 153 Pages: 438-450
  • Peer Reviewed
• [Journal Article] African lungfish, Protopterus annectens, possess an arginine vasotocin receptor homologous to the tetrapod V2-type receptor (2009)
  • Author(s): Nobufumi Konno, et al.
  • Journal Title: J.Exp.Biol. 212 Pages: 2183-2193
  • Peer Reviewed
• [Journal Article] Identification and genomic sequence of ghrelin receptor(GHS-R)-like receptor in the mozambique tilapia, Oreochromis mossambicus. (2009)
  • Author(s): Hiroyuki Kaiya, et al.
  • Journal Title: Zoolog. Sci. 26 Pages: 330-337
  • Peer Reviewed
• [Journal Article] Purification and properties of ghrelin from the intestine of the goldfish, Carassius auratus. (2009)
  • Author(s): Tohru Miura
  • Journal Title: Peptides. 30 Pages: 758-765
  • Peer Reviewed
• [Journal Article] Current knowledge of the roles of ghrelin in regulating food intake and energy balance in birds. (2009)
  • Author(s): Hiroyuki Kaiya, et al.
  • Journal Title: Gen.Comp.Endocrinol. 163 Pages: 33-38
  • Peer Reviewed
• [Journal Article] Purification and characterization of caprine ghrelin and its effect on growth hormone release.
  • Author(s): Takanori Ida, et al.
  • Journal Title: J.Mol.Neurosci. (in press)
  • Peer Reviewed