Hydrogen sulfide ameliorates high glucose-induced pro-inflammation factors in HT-22 cells: Involvement of SIRT1-mTOR/NF-κB signaling pathway

Hyperglycemia-induced neuroinflammation promotes the progression of diabetic encephalopathy. Hydrogen sulfide (H S) exerts anti-inflammatory and neuroprotective activities against neurodegenerative diseases. However, the effects of H S on hyperglycemia-induced neuroinflammation has not been investigated in neurons. Herein, by using HT-22 neuronal cells, we found that high glucose decreased the levels of endogenous H S and its catalytic enzyme, cystathionine-β-synthase (CBS). The administration of sodium hydrosulfide (NaHS, a H S donor) or S-adenosylmethionine (SAMe, an allosteric activator of CBS) restored high glucose-induced downregulation of CBS and H S levels. Importantly, H S ameliorated high glucose-induced inflammation in HT-22 cells, evidenced by NaHS or SAMe inhibited the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) expression in HT-22 cells exposed to high glucose. Furthermore, NaHS or SAMe restored the SIRT1 level and the phosphorylation of mTOR and NF-κB p65 disturbed by high glucose in HT-22 cells, suggesting H S reversed high glucose-induced alteration of SIRT1-mTOR/NF-κB signaling pathway. Our results demonstrated that exogenous H S treatment or enhancing endogenous H S synthesis prevents the inflammatory processes in the neurons with the exposure of high glucose. Therefore, increasing the H S level using NaHS or SAMe might shed light on the prophylactic treatment of diabetic encephalopathy. 2 2 2 2 2 2 2 2 2 2