Department of Stomatology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003,China.
Department of Stomatology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003,China.
Mol Immunol. 2018 Sep;101:312-318. doi: 10.1016/j.molimm.2018.07.009. Epub 2018 Jul 20.
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.
牙髓病变的进展是由免疫系统对细菌的反应所促进的，这增强了炎症调节因子的产生。细菌脂多糖（LPS）是所有革兰氏阴性菌细胞壁的主要结构成分，也是免疫系统的强效激活剂。细胞凋亡被认为在牙髓病变的炎症过程中起着重要作用。SIRT6 是组蛋白去乙酰化酶（HDACs）III 类的成员，也称为 SIRTs（沉默信息调节因子）。SIRT6 在牙髓病变中细胞凋亡中的作用尚不清楚。在这项研究中，我们发现 LPS 处理下调了人牙髓细胞（hDPCs）中 SIRT6 的表达。MTT 和 LDH 测定表明，hDPCs 中 SIRT6 的过表达减弱了 LPS 诱导的细胞死亡。一致地，我们的结果表明 SIRT6 能够保护 hDPCs 免受细胞凋亡。我们发现 SIRT6 可以通过免疫沉淀（IP）实验与 Ku70 相互作用，Ku70 是一种重要的凋亡调节剂。SIRT6 与 Ku70 物理结合。SIRT6 的过表达降低了 Ku70 的乙酰化水平，并促进了 Ku70 与促凋亡蛋白 Bax 的相互作用。这些研究强调了 SIRT6 在应激情况下 hDPCs 存活中的重要作用。
