Globular adiponectin inhibits angiotensin II-induced nuclear factor kappaB activation through AMP-activated protein kinase in cardiac hypertrophy.
Activation of nuclear factor kappaB (NF-kappaB) has been found necessary for cardiac hypertrophic growth in vivo and in vitro experiments. Adiponectin, an adipocyte-derived polypeptide, suppresses cardiac hypertrophy in response to pressure overload. Here we investigated the potential effect of adiponectin on NF-kappaB activation in hypertrophic neonatal rat ventricular myocytes (NRVMs) and related signal transduction pathway. We treated NRVMs with globular adiponectin (gAd) before angiotensin II (AngII) stimulation. Pretreating cells with gAd reduced the increased incorporation of [(3)H]-leucine and the mRNA levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) stimulated by AngII, indicating gAd inhibited AngII-induced cardiac hypertrophic signaling. Moreover, gAd pretreatment suppressed inhibitory protein kappaB (I-kappaB) phosphorylation and decreased p65 nuclear translocation, DNA-binding and transcription activity of NF-kappaB. Meanwhile, gAd promoted AMP-activated protein kinase (AMPK) phosphorylation, which is a downstream signaling mediator of adiponectin. Pharmacological activator of AMPK could inhibit AngII-induced NF-kappaB translocation, and inhibitor of AMPK or a dominant-negative AMPK adenovirus suppressed gAd-mediated inhibition of I-kappaB phosphorylation and NF-kappaB activation. When AMPK was inhibited, the suppressive effect of gAd on ANP mRNA expression was reduced. Our data indicate that gAd inhibits cardiac hypertrophic signaling through AMPK mediated suppression of NF-kappaB activation.
Key Laboratory of Molecular Cardiovascular Sciences, Department of Physiology and Pathophysiology, Peking University Health Science Center, Ministry of Education, Beijing, China.
Cheng
C
Wang
Li
L
Li
Zhi-Guo
ZG
Zhang
Dong
D
Fan
Yi
Y
Zhu
Li-Ling
LL
Wu
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006332:Cardiomegaly / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats
D052242:Adiponectin; D020672:I-kappa B Proteins; D016328:NF-kappa B; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D055372:AMP-Activated Protein Kinases