title: Adenosine monophosphate-activated protein kinase attenuates cardiomyocyte hypertrophy through regulation of FOXO3a/MAFbx signaling pathway.
abstract: Control of cardiac muscle mass is thought to be determined by a dynamic balance of protein synthesis and degradation. Recent studies have demonstrated that atrophy-related forkhead box O 3a (FOXO3a)/muscle atrophy F-box (MAFbx) signaling pathway plays a central role in the modulation of proteolysis and exert inhibitory effect on cardiomyocyte hypertrophy. In this study, we tested the hypothesis that adenosine monophosphate-activated protein kinase (AMPK) activation attenuates cardiomyocyte hypertrophy by regulating FOXO3a/MAFbx signaling pathway and its downstream protein degradation. The results showed that activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) attenuated cardiomyocyte hypertrophy induced by angiotensin II (Ang II). The antihypertrophic effects of AICAR were blunted by AMPK inhibitor Compound C. In addition, AMPK dramatically increased the activity of transcription factor FOXO3a, up-regulated the expression of its downstream ubiquitin ligase MAFbx, and enhanced cardiomyocyte proteolysis. Meanwhile, the effects of AMPK on protein degradation and cardiomyocyte hypertrophy were blocked after MAFbx was silenced by transfection of cardiomyocytes with MAFbx-siRNA. These results indicate that AMPK plays an important role in the inhibition of cardiomyocyte hypertrophy by activating protein degradation via FOXO3a/MAFbx signaling pathway.
authors: Department of Cardiology, The Guizhou Provincial People's Hospital, Guiyang 550002, China.
authors: Baolin
authors: B
authors: Chen
authors: Department of Cardiology, The Guizhou Provincial People's Hospital, Guiyang 550002, China hh792708016@qq.com.
authors: Qiang
authors: Q
authors: Wu
authors: Department of Cardiology, The Third Affiliated hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors: Zhaojun
authors: Z
authors: Xiong
authors: Department of Cardiology, The First Affiliated hospital of Sun Yat-Sen University, Guangzhou 510080, China Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors: Yuedong
authors: Y
authors: Ma
authors: Department of Cardiology, The Guizhou Provincial People's Hospital, Guiyang 550002, China.
authors: Sha
authors: S
authors: Yu
authors: Department of Cardiology, The Guizhou Provincial People's Hospital, Guiyang 550002, China.
authors: Dandan
authors: D
authors: Chen
authors: Department of Laboratory, The Guizhou Provincial People's Hospital, Guiyang 550002, China.
authors: Shengwen
authors: S
authors: Huang
authors: Department of Cardiology, The First Affiliated hospital of Sun Yat-Sen University, Guangzhou 510080, China Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors: Yugang
authors: Y
authors: Dong
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology; D044843:SKP Cullin F-Box Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide
keywords: adenosine monophosphate-activated protein kinase (AMPK); forkhead box O 3a (FOXO3a); hypertrophy; muscle atrophy F-box (MAFbx); ubiquitin-proteasome system