Protective effects of SIRT6 against lipopolysaccharide (LPS) are mediated by deacetylation of Ku70.

Highlights • The expression of SIRT6 in hDPCs was down-regulated by LPS. • Overexpression of SIRT6 in hDPCs attenuated cell death induced by LPS. • SIRT6 was able to protect hDPCs from apoptosis. • SIRT6 physically binds to Ku70. • SIRT6 promotes interaction of Ku70 with the proapoptotic protein Bax. Abstract Progression of pulpitis is facilitated by the immune system’s response to bacteria, enhancing the production of inflammatory regulators. Bacterial lipopolysaccharide (LPS) is the major structural component of the outer wall of all Gram-negative bacteria and a potent activator of the immune system. Apoptosis is believed to play an important role in the inflammatory process of pulpitis. SIRT6 is a member of class III of histone deacetylases (HDACs), also called sirtuins (SIRTs). The role of SIRT6 in apoptosis in pulpitis is unknown. In this study, we found that the expression of SIRT6 in human dental pulp cells (hDPCs) was down-regulated by treatment with LPS. MTT and LDH assays revealed that overexpression of SIRT6 in hDPCs attenuated cell death induced by LPS. Consistently, our results demonstrated that SIRT6 was able to protect hDPCs from apoptosis. We found that SIRT6 could interact with Ku70, an important apoptosis regulator, by the immunoprecipitation (IP) experiment. SIRT6 physically binds to Ku70. Overexpression of SIRT6 reduced acetylation of Ku70 and promoted interaction of Ku70 with the proapoptotic protein Bax. These studies underscore an essential role of SIRT6 in the survival of hDPCs in stress situations. [ABSTRACT FROM AUTHOR]