SIRT5 prevents mitochondrial dysfunction and cardiac hypertrophy induced by RIP140 | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 9، دوره 28، شماره 4، تیر 2025، صفحه 477-485 اصل مقاله (648.17 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2024.80343.17390 | ||
| نویسندگان | ||
| Liying Liang1؛ Yi Huang2؛ Qiujuan Wang1؛ Ye Hong1؛ Honghui Zhen1؛ Yanfang Chen* 1 | ||
| 1Department of Pharmacy, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China | ||
| 2Guangzhou Special Service Recuperation Center of PLA Rocket Force, Guangzhou, Guangdong, China | ||
| چکیده | ||
| 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. | ||
| کلیدواژهها | ||
| Cardiac hypertrophy؛ Energy metabolism؛ Mitochondria؛ RIP140؛ SIRT5 | ||
| مراجع | ||
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1. Hardt SE, Sadoshima J. Negative regulators of cardiac hypertrophy. Cardiovasc Res 2004; 63:500-509. 2. Martin TG, Juarros MA, Leinwand LA. Regression of cardiac hypertrophy in health and disease: Mechanisms and therapeutic potential. Nat Rev Cardiol 2023; 20:347-363. 3. Murphy E, Ardehali H, Balaban RS, DiLisa F, Dorn GW, 2nd, Kitsis RN, et al. Mitochondrial function, biology, and role in disease: A scientific statement from the american heart association. Circ Res 2016; 118: 1960-1991. 4. Wu J, Lu J, Huang J, You J, Ding Z, Ma L, et al. Variations in energy metabolism precede alterations in cardiac structure and function in hypertrophic preconditioning. Front Cardiovasc Med 2020; 7: 602100-602109. 5. Roe AT, Aronsen JM, Skardal K, Hamdani N, Linke WA, Danielsen HE, et al. Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular concentric hypertrophy. Cardiovasc Res 2017; 113: 1161-1172. 6. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 2005; 16: 4623-4635. 7. Gertz M, Steegborn C. Using mitochondrial sirtuins as drug targets: disease implications and available compounds. Cell Mol Life Sci 2016; 73: 2871-2896. 8. Newman JC, He W, Verdin E. Mitochondrial protein acylation and intermediary metabolism: Regulation by sirtuins and implications for metabolic disease. J Biol Chem 2012; 287: 42436-42443. 9. Yue Z, Ma Y, You J, Li Z, Ding Y, He P, et al. NMNAT3 is involved in the protective effect of SIRT3 in Ang II-induced cardiac hypertrophy. Exp Cell Res 2016; 347: 261-273. 10. Rardin MJ, He W, Nishida Y, Newman JC, Carrico C, Danielson SR, et al. SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab 2013; 18: 920-933. 11. Xiao ZP, Lv T, Hou PP, Manaenko A, Liu Y, Jin Y, et al. Sirtuin 5-Mediated Lysine Desuccinylation Protects Mitochondrial Metabolism Following Subarachnoid Hemorrhage in Mice. Stroke 2021; 52: 4043-4053. 12. Sadhukhan S, Liu X, Ryu D, Nelson OD, Stupinski JA, Li Z, et al. Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function. Proc Natl Acad Sci U S A 2016; 113: 4320-4325. 13. Gertz M, Steegborn C. Function and regulation of the mitochondrial sirtuin isoform Sirt5 in Mammalia. Biochim Biophys Acta 2010; 1804:1658-1665. 14. Liu B, Che W, Zheng C, Liu W, Wen J, Fu H, et al. SIRT5: A safeguard against oxidative stress-induced apoptosis in cardiomyocytes. Cell Physiol Biochem 2013; 32: 1050-1059. 15. Boylston JA, Sun J, Chen Y, Gucek M, Sack MN, Murphy E. Characterization of the cardiac succinylome and its role in ischemia-reperfusion injury. J Mol Cell Cardiol 2015; 88: 73-81. 16. Herzog B, Hallberg M, Seth A, Woods A, White R, Parker MG. The nuclear receptor cofactor, receptor-interacting protein 140, is required for the regulation of hepatic lipid and glucose metabolism by liver X receptor. Mol Endocrinol 2007; 21: 2687-2697. 17. Seth A, Steel JH, Nichol D, Pocock V, Kumaran MK, Fritah A, et al. The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle. Cell Metab 2007; 6: 236-245. 18. Chen Y, Chen S, Yue Z, Zhang Y, Zhou C, Cao W, et al. Receptor-interacting protein 140 overexpression impairs cardiac mitochondrial function and accelerates the transition to heart failure in chronically infarcted rats. Transl Res 2017; 180: 91-102. 19. Chen Y, Wang Y, Chen J, Chen X, Cao W, Chen S, et al. Roles of transcriptional corepressor RIP140 and coactivator PGC-1alpha in energy state of chronically infarcted rat hearts and mitochondrial function of cardiomyocytes. Mol Cell Endocrinol 2012; 362: 11-18. 20. Fritah A, Steel JH, Nichol D, Parker N, Williams S, Price A, et al. Elevated expression of the metabolic regulator receptor-interacting protein 140 results in cardiac hypertrophy and impaired cardiac function. Cardiovasc Res 2010; 86: 443-451. 21. Yamamoto T, Maurya SK, Pruzinsky E, Batmanov K, Xiao Y, Sulon SM, et al. RIP140 deficiency enhances cardiac fuel metabolism and protects mice from heart failure. J Clin Invest 2023; 133-146. 22. Buler M, Aatsinki SM, Izzi V, Uusimaa J, Hakkola J. SIRT5 is under the control of PGC-1alpha and AMPK and is involved in regulation of mitochondrial energy metabolism. FASEB J 2014; 28: 3225-3237. 23. Zhou SG, Zhou SF, Huang HQ, Chen JW, Huang M, Liu PQ. Proteomic analysis of hypertrophied myocardial protein patterns in renovascularly hypertensive and spontaneously hypertensive rats. J Proteome Res 2006; 5: 2901-2908. 24. Da Dalt L, Cabodevilla AG, Goldberg IJ, Norata GD. Cardiac lipid metabolism, mitochondrial function, and heart failure. Cardiovasc Res 2023; 119: 1905-1914. 25. Ng SM, Neubauer S, Rider OJ. Myocardial metabolism in heart failure. Curr Heart Fail Rep 2023; 20: 63-75. 26. Wasyluk W, Nowicka-Stazka P, Zwolak A. Heart metabolism in sepsis-induced cardiomyopathy-unusual metabolic dysfunction of the heart. Int J Environ Res Public Health 2021; 18: 7598-7618. 27. Bertero E, Maack C. Metabolic remodelling in heart failure. Nat Rev Cardiol 2018; 15: 457-470. 28. Zhou B, Tian R. Mitochondrial dysfunction in pathophysiology of heart failure. J Clin Invest 2018; 128: 3716-3726. 29. Doenst T, Nguyen TD, Abel ED. Cardiac metabolism in heart failure: Implications beyond ATP production. Circ Res 2013; 113: 709-724. 30. Long Q, Yang K, Yang Q. Regulation of mitochondrial ATP synthase in cardiac pathophysiology. Am J Cardiovasc Dis 2015; 5: 19-32. 31. Lu X, Yang P, Zhao X, Jiang M, Hu S, Ouyang Y, et al. OGDH mediates the inhibition of SIRT5 on cell proliferation and migration of gastric cancer. Exp Cell Res 2019; 382: 111483. 32. Meng T, Li FS, Xu D, Jing J, Li Z, Maimaitiaili M, et al. Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease. J Thorac Dis 2024; 16: 2326-2340. 33. Zhou L, Wang F, Sun R, Chen X, Zhang M, Xu Q, et al. SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense. EMBO Rep 2016; 17: 811-822. 34. Wei C, Shi M, Dong S, Li Z, Zhao B, Liu D, et al. SIRT5-related lysine demalonylation of GSTP1 contributes to cardiomyocyte pyroptosis suppression in diabetic cardiomyopathy. Int J Biol Sci 2024; 20: 585-605. 35. You J, Yue Z, Chen S, Chen Y, Lu X, Zhang X, et al. Receptor-interacting Protein 140 represses Sirtuin 3 to facilitate hypertrophy, mitochondrial dysfunction and energy metabolic dysfunction in cardiomyocytes. Acta Physiol (Oxf) 2017; 220: 58-71. 36. Zhang L, Chen Y, Yue Z, He Y, Zou J, Chen S, et al. The p65 subunit of NF-kappaB involves in RIP140-mediated inflammatory and metabolic dysregulation in cardiomyocytes. Arch Biochem Biophys 2014; 554: 22-27. | ||
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