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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.
Highlights
Cardiovascular disease shows the relatively higher levels of morbidity and mortality all over the world
Feno significantly decreased the cardiomyocyte apoptotic rate and the expression of cleaved caspase 3, but increased the ratio of Bcl-2/Bax (Figs 6B–E and 7B–E). These findings indicated that cardiomyocyte apoptosis might be suppressed by the activation of Peroxisome proliferator-activated receptor-a (PPARa) and Short-chain acyl-CoA dehydrogenase (SCAD)
The changes of SCAD in cardiomyocyte apoptosis was consistent with that in pathological cardiac hypertrophy we previously reported [10, 13]. These results indicated that SCAD may play an important role in cardiomyocyte apoptosis, which related with the transition of energy metabolism
Summary
Cardiovascular disease shows the relatively higher levels of morbidity and mortality all over the world. Large amount of evidence suggested that cardiomyocyte apoptosis played a critical role in the development of heart and numerous cardiac diseases [1, 2]. Cardiomyocyte apoptosis is a necessary process of transition from pathological cardiac hypertrophy to heart failure [3,4,5]. Short-chain acyl-CoA dehydrogenase (SCAD) is a member of acyl-CoA dehydrogenases family, which catalyses the Peroxisome proliferator-activated receptor-a (PPARa), a member of fatty acid-activated nuclear receptor family, was involved in the development of left ventrical hypertrophy and cardiomyocyte apoptosis [11, 12]. AMPK and PPARa is involved in the inhibition of gluconeogensis and fatty acid oxidation [16]. It has been shown that AMPK activation inhibited cardiac hypertrophy through the reactivation of PPARa signalling pathway [17]. We have previously shown that a 2016 The Authors
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