title: Role of adiponectin receptors in endothelin-induced cellular hypertrophy in cultured cardiomyocytes and their expression in infarcted heart.
abstract: Adiponectin, an adipocyte-derived protein, has cardioprotective actions. We elucidated the role of the adiponectin receptors AdipoR1 and AdipoR2 in the effects of adiponectin on endothelin-1 (ET-1)-induced hypertrophy in cultured cardiomyocytes, and we examined the expression of adiponectin receptors in normal and infarcted mouse hearts. Recombinant full-length adiponectin suppressed the ET-1-induced increase in cell surface area and [(3)H]leucine incorporation into cultured cardiomyocytes compared with cells treated with ET-1 alone. Transfection of small interfering RNA (siRNA) specific for AdipoR1 or AdipoR2 reversed the suppressive effects of adiponectin on ET-1-induced cellular hypertrophy in cultured cardiomyocytes. Adiponectin induced phosphorylation of AMP-activated protein kinase (AMPK) and inhibited ET-1-induced ERK1/2 phosphorylation, which were also reversible by transfection of siRNA for AdipoR1 or AdipoR2 in cultured cardiomyocytes. Transfection of siRNA for alpha(2)-catalytic subunits of AMPK reduced the inhibitory effects of adiponectin on ET-1-induced cellular hypertrophy and ERK1/2 phosphorylation. Effects of globular adiponectin were similar to those of full-length adiponectin, and siRNA for AdipoR1 reversed the actions of globular adiponectin. Compared with normal left ventricle, expression levels of AdipoR1 mRNA and protein were decreased in the remote, as well as the infarcted, area after myocardial infarction in mouse hearts. In conclusion, AdipoR1 and AdipoR2 mediate the suppressive effects of full-length and globular adiponectin on ET-1-induced hypertrophy in cultured cardiomyocytes, and AMPK is involved in signal transduction through these receptors. AdipoR1 and AdipoR2 might play a role in the pathogenesis of ET-1-related cardiomyocyte hypertrophy after myocardial infarction.
authors.affiliation: Department of Internal Medicine II, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Nakakoma-gun, Yamanashi 409-3898, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujioka
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saito
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kodama
authors.forename: Hajime
authors.initials: H
authors.lastname: Takano
authors.forename: Jyun-ei
authors.initials: JE
authors.lastname: Obata
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kitta
authors.forename: Ken
authors.initials: K
authors.lastname: Umetani
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kugiyama
mesh_terms: D052242:Adiponectin / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000503:physiopathology; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D019332:Endothelin-1; D016232:Endothelins; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; D000804:Angiotensin II; D009638:Norepinephrine