Int J Med Sci 2020; 17(3):310-319. doi:10.7150/ijms.38602

Research Paper

Hydrogen Sulfide Inhibits Homocysteine-Induced Neuronal Senescence by Up-Regulation of SIRT1

Xuan Kang1,2*, Cheng Li2,3*, Xi Xie2,4*, Ke-Bin Zhan2,4✉, San-Qiao Yang1,2, Yi-Yun Tang2, Wei Zou2,5, Ping Zhang2,5, Xiao-Qing Tang1,2✉

1. Institute of Neurology, the First Affiliated Hospital, University of South China, Hengyang, 42100, Hunan, P.R. China.
2. Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, 42100, Hunan, P.R. China.
3. Department of Emergency, Affiliated Nanhua Hospital, University of South China, Hengyang, 421001, Hunan, P. R. China.
4. Department of Neurology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, P.R. China.
5. Department of Neurology, Affiliated Nanhua Hospital, University of South China, Hengyang, 421001, Hunan, P. R. China.
*Xuan Kang, Cheng Li and Xi Xie contributed equally to this work.

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Citation:
Kang X, Li C, Xie X, Zhan KB, Yang SQ, Tang YY, Zou W, Zhang P, Tang XQ. Hydrogen Sulfide Inhibits Homocysteine-Induced Neuronal Senescence by Up-Regulation of SIRT1. Int J Med Sci 2020; 17(3):310-319. doi:10.7150/ijms.38602. Available from http://www.medsci.org/v17p0310.htm

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Abstract

Homocysteine (Hcy) accelerates neuronal senescence and induces age-related neurodegenerative diseases. Silence signal regulating factor 1 (SIRT1) prolongs lifespan and takes neuroprotective effects. We have previously demonstrated that hydrogen sulfide (H2S) prevents Hcy-induced apoptosis of neuronal cells and has neuroprotective effect. In the present work, we aimed to investigate whether H2S protects HT22 cells against Hcy-induced neuronal senescence and whether SIRT1 mediates this role of H2S. We found that Hcy induced cellular senescence in HT22 cells, as determined by β-galactosidase staining, expressions of P16INK4a, P21CIPL, and trypan blue Staining, which are the markers of cellular senescence. However, sodium hydrosulfide (NaHS, the donor of H2S) significantly reversed Hcy-induced cellular senescence. Interestingly, NaHS not only up-regulated the expression of SIRT1 in HT22 cells but also reversed Hcy-downregulated the expression of SIRT1 in HT22 cells. Furthermore, we found that pretreatment with Sirtinol (an inhibitor of SIRT1) markedly reversed the protection of NaHS against Hcy-induced HT22 cells senescence and apoptosis. Our findings illustrated that H2S protects HT22 cells against Hcy-induced senescence by up-regulating SIRT1.

Keywords: cell senescence, homocysteine, hydrogen sulfide, SIRT1