title: Effects of short-chain acyl-CoA dehydrogenase on cardiomyocyte apoptosis.
abstract: Short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme of fatty acid β-oxidation, plays an important role in cardiac hypertrophy. However, its effect on the cardiomyocyte apoptosis remains unknown. We aimed to determine the role of SCAD in tert-butyl hydroperoxide (tBHP)-induced cardiomyocyte apoptosis. The mRNA and protein expression of SCAD were significantly down-regulated in the cardiomyocyte apoptosis model. Inhibition of SCAD with siRNA-1186 significantly decreased SCAD expression, enzyme activity and ATP content, but obviously increased the content of free fatty acids. Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP, such as the increase in cell apoptotic rate, the activation of caspase3 and the decrease in the Bcl-2/Bax ratio, which showed that SCAD may play an important role in primary cardiomyocyte apoptosis. The changes of phosphonate AMP-activated protein kinase α (p-AMPKα) and Peroxisome proliferator-activated receptor α (PPARα) in cardiomyocyte apoptosis were consistent with that of SCAD. Furthermore, PPARα activator fenofibrate and AMPKα activator AICAR treatment significantly increased the expression of SCAD and inhibited cardiomyocyte apoptosis. In conclusion, for the first time our findings directly demonstrated that SCAD may be as a new target to prevent cardiomyocyte apoptosis through the AMPK/PPARα/SCAD signal pathways.
authors.affiliation: Department of Clinical Pharmacy, GuangDong Pharmaceutical University, Guangzhou, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Clinical Pharmacy, GuangDong Pharmaceutical University, Guangzhou, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacy, GuangDong Pharmaceutical University, Guangzhou, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Shu
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shaorui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacy, GuangDong Pharmaceutical University, Guangzhou, China.
authors.forename: Xuediao
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Clinical Pharmacy, GuangDong Pharmaceutical University, Guangzhou, China.
authors.forename: Linquan
authors.initials: L
authors.lastname: Zang
authors.affiliation: Department of Clinical Pharmacy, GuangDong Pharmaceutical University, Guangzhou, China.
authors.forename: Sigui
authors.initials: S
authors.lastname: Zhou
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D044926:Butyryl-CoA Dehydrogenase / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D011345:Fenofibrate / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D047493:PPAR alpha / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012265:Ribonucleotides / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D047493:PPAR alpha; D034741:RNA, Small Interfering; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D020122:tert-Butylhydroperoxide; D044926:Butyryl-CoA Dehydrogenase; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D011345:Fenofibrate
keywords: AMP-activated protein kinase; cardiomyocyte apoptosis; energy metabolism•; peroxisome proliferator-activated receptor α; short-chain acyl-CoA dehydrogenase; tert-butyl hydroperoxide