ABSTRACT
[Objective]To investigate the effect of desuccinylase Sirtuin5 (SIRT5) on receptor-interacting protein 140 (RIP140)- mediated metabolic dysfunction in cardiomyocytes.[Methods]RIP140 was overexpressed by Adenovirus infection and SIRT5 was overexpressed by plasmid transfection. RIP140 and SIRT5 were knocked down by siRNA interference. The expression of RIP140 and SIRT5 were measured by qRT-PCR and western blot. The transcription levels of mitochondrial DNA-encoded genes were detected by qRT-PCR. Mitochondrial membrane potential was detected by tetramethylrhodamine ethyl ester(TMRE)fluorescence anl?ysis. Cellular oxygen consumption and ATP production were investigated by assay kits. All data are from at least three independent ex?periments.[Results]RIP140 overexpression significantly attenuated SIRT5 expression(P<0.05),whereas knockdown of endogenous RIP140 elevated SIRT5 expression(P<0.05)in cardiomyocytes. Superabundant RIP140 also induced hypersuccinylation of mitochon?drial proteins,suggesting RIP140 could repress the desuccinylase activity of SIRT5. Moreover,SIRT5 overexpression reversed RIP140-mediated mitochondrial dysfunction and energy metabolic impairment ,such as repression of mitochondrial DNA-encoded genes(P<0.05),decrease of mitochondrial membrane potential(P<0.05),as well as reduction of cellular oxygen consumption(P<0.05)and ATP production(P<0.05). Furthermore,the regulation of RIP140 on SIRT5 was dependent on the peroxisome proliferator-activated receptorα(PPARα)in cardiomyocytes.[Conclusion]RIP140 induces mitochondrial dysfunction and metabolic impairment through repression of SIRT5 in cardiomyocytes.
ABSTRACT
Obstructive sleep apnea syndrome (OSAS) is a prevalent disorder that has been reported to occur in 2 to 4% of middle-aged adults. A similar prevalence of OSAS has been reported from India as well. However, this condition is frequently unrecognized and underdiagnosed. Important pathophysiological changes in patients with obstructive sleep apnea (OSA) is an alteration in human upper airway leading to a reduction in cross-sectional area of the upper airway contributing to the easy collapsibility of upper airway during sleep. Other pathophysiological changes in OSA are oxidative stress, systemic inflammation, sympathetic nerve activation, endothelial dysfunction, procoagulant activity, intrathoracic pressure changes and metabolic dysregulation. The gold standard for diagnosis of OSA is full polysomnography.