title: CSE/H2S system protects mesenchymal stem cells from hypoxia and serum deprivation‑induced apoptosis via mitochondrial injury, endoplasmic reticulum stress and PI3K/Akt activation pathways.
abstract: Mesenchymal stem cells (MSCs) have the potential to facilitate cardiac repair following acute myocardial infarction. However, MSC therapy is limited by apoptosis of the stem cells following transplantation. 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 mechanism underlying the antiapoptotic effect of the endogenous cystathionine γ-lyase (CSE)/H2S system in MSCs cultivated in conditions of hypoxia and serum deprivation (H/SD). Western blotting was performed in order to determine the expression of proteins associated with the mitochondrial injury pathway, endoplasmic reticulum stress and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. It was demonstrated that H/SD is able to significantly induce apoptosis in MSCs. CSE overexpression, which enhances the endogenous H2S level, protects MSCs from H/SD-induced apoptosis via attenuation of the mitochondrial injury pathway, inhibition of endoplasmic reticulum stress and activation of the PI3K/Akt signaling pathway. In conclusion, the present findings suggest that modulation of the CSE/H2S system may a therapeutic approach with which to promote the viability of transplanted MSCs.
authors.affiliation: Department of ICU, Anhui No. 2 Provincial People's Hospital, Hefei, Anhui 230041, P.R. China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Cong Sheng
authors.initials: CS
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Chun Miao
authors.initials: CM
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Yang Jing
authors.initials: YJ
authors.lastname: Xie
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Ai Ling
authors.initials: AL
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D006862:Hydrogen Sulfide / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide