Role of sumoylation modification of sirtuin 3 in hypertension-associated

Abstract Objective The present study was designed to investigate whether mitochondrial dysfunction and oxidative stress in HTN-injured cardiomyocytes are associated with SIRT3 SUMOylation and whether SIRT3 deSUMOylation can ameliorate the related cardiomyocyte injury. Design and method The human cardiomyocyte AC16 cell line was used for the study. The SIRT3-K288R cell line was constructed by lentiviral transfection;The expression of SOD2, acetyl-SOD2 (MnSOD), protein acetylation level, inflammatory vesicle NLRP3, etc. in different subgroups were detected by Western Blot, and the roles of SUMOylation modification and SIRT3 deacetylation in HTN-associated cell injury were investigated by flow cytometry. Results (1) Western Blot results showed that compared to the HTN cell injury model, the cardiomyocytes in the SIRT3-K288R intervention group had increased Acetyl- SOD2/SOD2 levels were increased (p < 0.05) and protein acetylation levels were decreased in the SIRT3-K288R intervention group compared with the HTN cell injury model, indicating that SIRT3 increased the deacetylation effect on mitochondria and increased cellular antioxidant stress enzyme activity; (2) Western Blot results showed that compared with the HTN cell injury model, cardiomyocytes in the SIRT3-K288R intervention group NLRP3 and NOX4 levels were significantly reduced, indicating that SIRT3 deSUMOylation could improve the inflammatory response to Ang-II-related cell injury. (3) Flow cytometry results showed that K288R transfection ameliorated the reduction of cellular membrane potential, suggesting that deSUMOylation modification of SIRT3 reduces Ang-II damage to mitochondrial membrane potential. Conclusions In the HTN-associated cell injury model, the removal of SUMOylation modification by viral transfection could improve oxidative stress, protein acetylation levels and associated inflammatory responses in HTN-injured cardiomyocytes, indicating that SIRT3 SUMOylation may play an important mechanism in HTN-associated cell injury, and reducing SIRT3 SUMOylation modification may be a possible direction for future research.