SIRT1 attenuated oxidative stress induced by methyl tert-butyl ether in HT22 cells.

Methyl tertiary-butyl ether (MTBE), an unleaded gasoline additive, can lead to oxidative stress, thus injuring the nervous system after long-term exposure. SIRT1, a NAD+-dependent histone deacetylase, can play a neuroprotective role in brain injury. However, the mechanism is unclear. This present study intended to define the role of SIRT1 during the process of MTBE-induced oxidative stress in mouse hippocampal neurons (HT22 cells). Our data showed that MTBE could directly trigger oxidative stress in HT22 cells by decreasing the activity of superoxide dismutase (SOD) and GSH/T-GSH level while increasing ROS, lipid peroxidation product malondialdehyde (MDA) and GSSG level. Similarly, the expression of SIRT1, an antioxidant, decreased in a dose-dependent manner. To further explore whether SIRT1 plays a key role during the process of oxidative stress, HT22 cells were transfected with siRNA-SIRT1 and preconditioned with the agonist of SIRT1 (SRT1720) for 2 h. The levels of oxidative stress (ROS, SOD, MDA, GSH/GSSG) were detected again after siRNA-SIRT1 HT22 cells and SRT1720 HT22 cells were exposed to MTBE for 6 h. In contrast to the non-pretreated group, levels of oxidative stress were tonic in siRNA-SIRT1 HT22 cells and attenuated in SRT1720 HT22 cells. Our results indicate that MTBE could directly cause oxidative stress in HT-22 cells, and SIRT1 might be an important antioxidant during MTBE-induced oxidative stress.