SIRT6 protects against lipopolysaccharide (LPS)-induced apoptosis in human dental pulp cells by deacetylation of Ku70.

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, terminal transferase dUTP nick end labeling (TUNEL) assay 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 and deacetylates it, and this promotes interaction of Ku70 with the proapoptotic protein Bax. These studies underscore an essential role of SIRT6 in the survival of hDPCs in stress situations.