Adenosine monophosphate-activated protein kinase attenuates cardiomyocyte hypertrophy through regulation of FOXO3a/MAFbx signaling pathway  

作　　者：Baolin Chen Qiang WU Zhaojun Xiong Yuedong Ma Sha Yu Dandan Chen Shengwen Huang Yugang Dong 

机构地区：[1]Department of Cardiology, The Guizhou Provincial People's Hospital, Guiyang 550002, China [2]Department ofCardiology, The Third Affiliated hospital of Sun Yat-Sen University, Buangzhou 510080, China [3]DePartment ofCardiology, The First Affiliated hospital of Sun Yat-Sen University, Guangzhou 510080, China [4]Key Laboratory onAssisted Circulation, Ministry of Health, Buangzhou 510080, China [5]Department of Laboratory, The GuizhouPrevincial People's Hospital, Guiyang 550002, China

出　　处：《Acta Biochimica et Biophysica Sinica》2016年第9期827-832,共6页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China （No. 30971260） and the Guizhou Provincial Science and Technology Department Fund of China （No. Qian[2011]2247）.

摘　　要：Control of cardiac muscle mass is thought to be determined by a dynamic balance of protein synthe- sis 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 Iigase 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.Control of cardiac muscle mass is thought to be determined by a dynamic balance of protein synthe- sis 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 Iigase 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.

关 键 词：adenosine monophosphate-activated protein kinase （AMPK） forkhead box O3a （FOXO3a） HYPERTROPHY muscleatrophy F-box （MAFbx） ubiquitin-proteasome system 

分 类 号：Q[生物学]