Li Congsheng, Guo Zeng, Guo Birong, Xie Yangjing, Yang Jing, Wang Ailing
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
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.
Mol Med Rep. 2014 Jun;9(6):2467-72. doi: 10.3892/mmr.2014.2111. Epub 2014 Apr 3.
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.
间充质干细胞（MSCs）在急性心肌梗死后的修复方面具有巨大潜力。然而，MSC治疗面临的一个主要挑战是移植细胞会发生凋亡。硫化氢（H2S）最近被认为是各种系统中细胞凋亡的内源性介质。本研究的目的是探讨内源性H2S在缺氧和血清剥夺（缺氧/SD）诱导的MSCs凋亡中的作用。本研究表明，将MSCs暴露于缺氧/SD会导致H2S生成显著减少，并导致明显的细胞凋亡。此外，在基础条件下，MSCs表达胱硫醚γ-裂解酶（CSE）并合成H2S，而缺氧/SD处理会抑制CSE的表达和活性。CSE的过表达不仅显著阻止了缺氧/SD诱导的内源性H2S生成减少，还保护MSCs免于凋亡，而其强效抑制剂对CSE的抑制则显著恶化了缺氧/SD对MSCs的影响。这些数据表明，H2S生成途径存在于MSCs中，内源性CSE/H2S系统的抑制促成了缺氧/SD诱导的MSCs凋亡。我们的研究结果表明，调节CSE/H2S系统是促进移植MSCs存活的潜在治疗途径。
