Hydrogen sulfide delays nicotinamide-induced premature senescence via upregulation of SIRT1 in human umbilical vein endothelial cells

Mol Cell Biochem. 2014 Aug;393(1-2):59-67. doi: 10.1007/s11010-014-2046-y. Epub 2014 Apr 13.


The present study was designed to investigate the effect of hydrogen sulfide on cellular senescence of human umbilical vascular endothelial cells (HUVECs CC-2517) and its underlying mechanism. The premature senescence-like phenotype HUVECs (the fourth passage) was induced by treatment with nicotinamide (NAM, an inhibitor of SIRT1, 5 mmol/L, 12 h). Cells were cultured with sodium hydrosulfide (NaHS, 12.5, 25, 50 and 100 μmol/L) for 48 h in premature senescence-like phenotype HUVECs. The fourth passage of HUVECs was considered as young group. Senescence-associated (SA)-β-galactosidase activities were detected to evaluate cell senescence, and the expression of SA heterochromatin foci (SAHF) was visualized by DAPI DNA staining. The mRNA and protein levels of SIRT1 were detected using RT-PCR and western blotting analysis, respectively. The results showed that β-galactosidase positive cells and the formation of SAHF were markedly increased after treatment with NAM (5 mmol/L) for 12 h. We also found that NaHS (12.5 μmol/L) had no effect on the percentage of SA β-gal positive cells and the expression of SAHF, and the hallmarks decreased at the concentration of 25 and 50 μmol/L, reaching the minimum at 50 μmol/L, while the percentage of SA β-gal positive cells and the expression of SAHF increased at the concentration of 100 μmol/L. Furthermore, we found that both on protein and mRNA levels of SIRT1 in the Y+N+S50 group was significantly increased compared with that in Y+N group. In conclusion, NaHS delays senescence of HUVECs induced by NAM via upregulation of SIRT1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects*
  • Aging / pathology
  • Cellular Senescence / drug effects*
  • Gene Expression Regulation / drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogen Peroxide / metabolism
  • Hydrogen Sulfide / administration & dosage*
  • Niacinamide / administration & dosage
  • RNA, Messenger / biosynthesis
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / biosynthesis*
  • Transcriptional Activation


  • RNA, Messenger
  • Niacinamide
  • Hydrogen Peroxide
  • SIRT1 protein, human
  • Sirtuin 1
  • Hydrogen Sulfide