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

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

  • Int Immunopharmacol. 2021 Jun;95:107545. doi: 10.1016/j.intimp.2021.107545.
Xinrui Li 1 Peiquan Yu 1 Yinghua Yu 2 Ting Xu 1 Jiao Liu 1 Yuan Cheng 1 Xia Yang 1 Xiaoying Cui 3 Cui Yin 4 Yi Liu 5
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
  • 2 Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Illawarra Health and Medical Research Institute, School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia.
  • 3 Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4113, Australia.
  • 4 Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
  • 5 Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address: [email protected].
Abstract

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.

Keywords

Diabetic encephalopathy; H(2)S; HT-22 cells; Neuroinflammation; SIRT1-mTOR/NF-κB.

Figures
Products