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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mol. Neurosci. | doi: 10.3389/fnmol.2019.00194

Hydrogen sulfide inhibits high glucose-induced neuronal senescence by improving autophagic flux via up-regulation of SIRT1

Lei Wu1, Ying Chen1,  Chun-Yan Wang2, Yi-Yun Tang2, Hong-Lin Huang1*, Xun Kang3, xiang li3, Yu-Rong Xie4 and  Xiao-Qing Tang2*
  • 1Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, China
  • 2Institute of Neuroscience, Hengyang Medical College, University of South China, China
  • 3Department of Neurology, First Affiliated Hospital of University of South China, China
  • 4College of Chemistry and Chemical Engineering, University of South China, China

Hyperglycemia, a key characteristic and risk factor for diabetes mellitus (DM), causes neuronal senescence. Hydrogen sulfide (H2S) is a novel neuroprotectant. The present work was to investigate the potential effect of H2S on hyperglycemia-induced neuronal senescence and the underlying mechanisms. We found that NaHS, a donor of H2S, inhibited high glucose (HG)-induced cellular senescence in HT22 cells (an immortalized mouse hippocampal cell line), as evidenced by decrease in the number of SA-β-gal positive cells, increase in the cells growth, and down-regulations of senescence mark proteins, p16INK4a and p21CIP1. NaHS improved the autophagic flux, which is judged by decrease in the amount of intracellular autophagosome as well as up-regulations of LC3II/I and P62 in HG-exposed HT22 cells. Furthermore, blocked autophagic flux by chloroquine (CQ) significantly abolished NaHS-exerted improvement in the autophagic flux and suppression in the cellular senescence of GH-exposed HT22 cells, which indicated that H2S antagonizes HG-induced neuronal senescence by promoting autophagic flux. We also found that NaHS up-regulated the expression of silent mating type information regulation 2 homolog 1 (SIRT1), an important anti-aging protein, in HG-exposed HT22 cells. Furthermore, inhibition of SIRT1 by sirtinol reversed the protection of H2S against HG-induced autophagic flux blockade and cellular senescence in HT22 cells. These data indicated that H2S protects HT22 cells against HG-induced cellular senescence by improving autophagic flux via up-regulation of SIRT1, suggesting H2S as a potential treatment strategy for hyperglycemia-induced neuronal senescence and neurotoxicity.

Keywords: Hydrogen Sulfide, high glucose, SIRT1, Autophagic Flux, Neuronal senescence

Received: 01 May 2019; Accepted: 25 Jul 2019.

Edited by:

Claudio Grassi, Catholic University of the Sacred Heart, Italy

Reviewed by:

Eva M. Jimenez-Mateos, Trinity College Dublin, Ireland
Salvatore Fusco, Agostino Gemelli University Polyclinic, Italy  

Copyright: © 2019 Wu, Chen, Wang, Tang, Huang, Kang, li, Xie and Tang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Hong-Lin Huang, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan Province, China, huanghl@usc.edu.cn
Prof. Xiao-Qing Tang, Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, Hunan Province, China, tangxq-usc@qq.com