SIRT5 prevents mitochondrial dysfunction and cardiac hypertrophy induced by RIP140

Document Type : Original Article

Authors

1 Department of Pharmacy, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China

2 Guangzhou Special Service Recuperation Center of PLA Rocket Force, Guangzhou, Guangdong, China

Abstract

Objective(s): To investigate the effect and mechanism of Sirtuin5 (SIRT5) on mitochondrial dysfunction and cardiac hypertrophy induced by receptor-interacting protein 140 (RIP140).
Materials and Methods: The neonatal rat cardiomyocytes (NRCMs) and SD rats were treated with Angiotensin II (Ang II) to induce in vitro and in vivo model of cardiac hypertrophy. 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, SIRT5, and biomarkers of cardiac hypertrophy were measured by qRT-PCR and western blot. The transcription levels of mitochondrial DNA-encoded genes were detected by qRT-PCR. Cell surface area and mitochondrial membrane potential were respectively detected by rhodamine-phalloidin and tetramethylrhodamine ethyl ester (TMRE) fluorescence analysis. Cellular oxygen consumption and ATP production were investigated using assay kits. All data are from at least three independent experiments.
Results: The expression of SIRT5 was down-regulated in NRCMs and hearts treated with Ang II. Overexpression of SIRT5 protected cardiomyocytes from AngII-induced hypertrophy, whereas knockdown of SIRT5 resulted in cardiac hypertrophy. Moreover, since SIRT5 was regulated by the transcriptional coactivator, we also found that SIRT5 could be negatively regulated by the transcriptional corepressor RIP140 in cardiomyocytes. Furthermore, SIRT5 significantly attenuated energy metabolic dysregulation and mitochondrial dysfunction and exerted its protective role on myocardial hypertrophy under the regulation of RIP140.
Conclusion: SIRT5 exerts a protective role in mitochondrial dysfunction and cardiac hypertrophy induced by RIP140.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 28, Issue 4
April 2025
Pages 477-485

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