Inhibition of the endogenous CSE/H₂S system contributes to hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells.
Mesenchymal stem cells (MSCs) have great potential for repair following acute myocardial infarction. However, a major challenge to MSC therapy is that transplanted cells undergo apoptosis. Hydrogen sulfide (H2S) has recently been proposed as an endogenous mediator of cell apoptosis in various systems. The aim of the present study was to investigate the role of endogenous H2S in hypoxia and serum deprivation (hypoxia/SD)-induced apoptosis in MSCs. The present study demonstrated that exposure of MSCs to hypoxia/SD caused a significant decrease in H2S generation and resulted in marked cell apoptosis. Furthermore, under basal conditions, MSCs expressed cystathionine γ-lyase (CSE) and synthesized H2S, whereas CSE expression and activity was inhibited by hypoxia/SD treatment. Overexpression of CSE not only markedly prevented hypoxia/SD-induced decreases in endogenous H2S generation but also protected MSCs from apoptosis, while inhibition of CSE by its potent inhibitors significantly deteriorated the effect of hypoxia/SD in MSCs. These data indicate that the H2S generation pathway exists in MSCs and the inhibition of the endogenous CSE/H2S system contributes to hypoxia/SD-induced apoptosis in MSCs. Our findings suggest that modulation of the CSE/H2S system is a potential therapeutic avenue for promoting the viability of transplanted MSCs.
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Congsheng
C
Li
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Zeng
Z
Guo
Department of Dermatology, The Third Affiliated Hospital of Anhui Medical University and the First People's Hospital of Hefei, Hefei, Anhui 230061, P.R. China.
Birong
B
Guo
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Yangjing
Y
Xie
Department of Emergency, The Third Affiliated Hospital of Anhui Medical University and the First People's Hospital of Hefei, Hefei, Anhui 230061, P.R. China.
Jing
J
Yang
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Ailing
A
Wang
D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051381:Rats
D000480:Alkynes; C009055:propargylglycine; D003542:Cystathionine gamma-Lyase; D005998:Glycine; D006862:Hydrogen Sulfide