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 (H2S) exerts anti-inflammatory and neuroprotective activities against neurodegenerative diseases. However, the effects of H2S 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 H2S and its catalytic enzyme, cystathionine-β-synthase (CBS). The administration of sodium hydrosulfide (NaHS, a H2S donor) or S-adenosylmethionine (SAMe, an allosteric activator of CBS) restored high glucose-induced downregulation of CBS and H2S levels. Importantly, H2S 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 H2S reversed high glucose-induced alteration of SIRT1-mTOR/NF-κB signaling pathway. Our results demonstrated that exogenous H2S treatment or enhancing endogenous H2S synthesis prevents the inflammatory processes in the neurons with the exposure of high glucose. Therefore, increasing the H2S level using NaHS or SAMe might shed light on the prophylactic treatment of diabetic encephalopathy.