科研之友
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摘要
Background. Hydrogen sulfide (H2S) is an endogenously generated gaseous transmitter known for its cytoprotective effect mediated by the PI3K-Akt signaling pathway. Human induced pluripotent stem cell (hiPSC) derived mesenchymal stromal cells (MSCs), or hiPSC-MSCs, represent an alternative source of MSCs for autologous cell therapy. The big-conductance Ca2+-activated outward K currents (BKca), known to mediate cell proliferation, have been detected in >80% of hiPSC-MSCs. The present study aimed to explore the effect of H2S on survival and proliferation of hiPSC-MSCs and investigate the mediatory role of BKca. Methods. Effects of H2S on proliferation and survival of hiPSC-MSCs were measured by 5-bromo-2-deoxyuridine incorporation, population doubling and cell cycle assays, and by 3-(4,5)-dimethylthiahiazo(-z-y1)3,5-di-phenytetrazoliumromide assay and 4'-6-diamidino-2-phenylindole staining, respectively. BKca was recorded by means of the whole-cell patch-clamp technique. The expressions of KCa 1.1 (encoding BKca) and apoptosis-related genes were measured by reverse transcriptase polymerase chain reaction. The phosphorylation of Akt was assessed by Western blot analysis. Results. Exogenously administered NaHS (an H2S donor, 50-300 mu mol/L) significantly promoted proliferation of hiPSC-MSCs. NaHS prevented the hypoxia-induced apoptosis and suppressed BKca currents without altering the expression levels of alpha- and beta-KCa 1.1. In addition, NaHS increased the phosphorylation of Akt and decreased the expression of Caspase 8 and Bax in hiPSC-MSCs. Paxilline (1 mu mol/L), a BKca blocker, showed similar effects on promoting cell proliferation and phosphorylation of Akt and suppression of apoptotic genes in hiPSC-MSCs. Conclusions. Our data confirmed that H2S arguments the proliferation and survival of hiPSC-MSCs through activation of the PI3K-Akt pathway and that such effects could be mediated through inhibition of BKca.
- 出版日期2013-11
- 单位中国药科大学
