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Hydrogen Sulfide Inhibits Formaldehyde-Induced Senescence in HT-22 Cells via Upregulation of Leptin Signaling

  • Wei-Wen Zhu
  • Min Ning
  • Yi-Zhu Peng
  • Yi-Yun Tang
  • Xuan Kang
  • Ke-Bin ZhanEmail author
  • Wei Zou
  • Ping Zhang
  • Xiao-Qing TangEmail author
Original Paper
  • 45 Downloads

Abstract

It has been previously demonstrated that hydrogen sulfide (H2S) prevents formaldehyde (FA)-induced neurotoxicity. However, the exact mechanisms underlying this protection remain to be fully elucidated. Neuronal senescence is involved in FA-induced neurotoxicity. Leptin signaling has anti-aging function. The present work was to investigate the protection of H2S against FA-induced neuronal senescence and the mediatory role of leptin signaling. FA-exposed HT-22 cells were used as the vitro model of FA-induced neuronal senescence. The senescence-associated β-galactosidase (SA-β-Gal) positive cell was detected by β-galactosidase staining. The expressions of P16INK4a, P21CIP1, leptin, and lepRb (leptin receptor) were measured by western blot. The proliferation, viability, and apoptosis of cells were evaluated by Trypan blue exclusion assay, Cell Counting Kit-8 (CCK-8) assay, and Flow cytometry analysis, respectively. We found that H2S suppressed FA-induced senescence, as evidenced by the decrease in SA-β-Gal positive cells, the downregulations of P16INK4a and P21CIP1, as well as decrease in cell growth arrest, in HT-22 cells. Also, H2S upregulated the expressions of leptin and lepRb in FA-exposed HT-22 cells. Furthermore, leptin tA (a specific inhibitor of the leptin) abolished the protective effects of H2S on FA-induced senescence and neurotoxicity (as evidenced by the increase in cell viability and the decrease in cell apoptosis) in HT-22 cells. These results indicated that H2S prevents FA-induced neuronal senescence via upregulation of leptin signaling. Our findings offer a novel insight into the mechanisms underlying the protection of H2S against FA-induced neurotoxicity.

Graphical Abstract

FA upregulates the expressions of P16INK4a and P21CIP1 via inhibiting leptin signaling, which in turn induces senescence in HT-22 cells; H2S downregulates the expressions of P16INK4a and P21CIP1 via reversing FA-downregulated leptin signaling, which in turn prevents FA-induced senescence in HT-22 cells.

Keywords

Formaldehyde Senescence Hydrogen sulfide Leptin signaling 

Notes

Acknowledgements

This study is supported by Natural Science Foundation of China (81671057), the Major Research Topics of the Health and Family Planning Commission of Hunan province (A2017011), Hunan Provincial Innovation Foundation for Postgraduate (CX2017B570, CX2018B619) and Postgraduate Research Innovation Foundation of University of South China (2018KYZ048).

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Wei-Wen Zhu
    • 1
  • Min Ning
    • 1
    • 2
  • Yi-Zhu Peng
    • 1
    • 2
  • Yi-Yun Tang
    • 1
  • Xuan Kang
    • 1
    • 3
  • Ke-Bin Zhan
    • 1
    • 2
    Email author
  • Wei Zou
    • 1
    • 4
  • Ping Zhang
    • 1
    • 4
  • Xiao-Qing Tang
    • 1
    • 5
    Email author
  1. 1.Institute of Neuroscience, Hengyang Medical CollegeUniversity of South ChinaHengyangPeople’s Republic of China
  2. 2.Department of Neurology, The Second Affiliated HospitalUniversity of South ChinaHengyangPeople’s Republic of China
  3. 3.Department of Endocrinology, The First Affiliated HospitalUniversity of South ChinaHengyangPeople’s Republic of China
  4. 4.Department of Neurology, Affiliated Nanhua HospitalUniversity of South ChinaHengyangPeople’s Republic of China
  5. 5.Institute of Neurology, The First Affiliated HospitalUniversity of South ChinaHengyangPeople’s Republic of China

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