ERK1/2 pathway mediates the protective effect of hydrogen sulfide against cisplatin-induced injury in human marrow mesenchymai stem cells

Objective To explore the protection and mechanism of hydrogen sulfide （H2S） preconditioning against injury induced by cisplatin in human marrow mesenchymal stem cells （HMMSCs）. Methods HMMSCs were treated by cisplatin at 0, 5, 10, 20, 40, 60, 80 mg/L concentrations for 24 h respectively and were exposed to eisplatin at 20 mg/L concentrations for 0, 6, 12, 24, 36, 48 h respectively. HMMSCs were pretreated with NariS at 0, 0.4, 0.6, 0.8, 1.0 mmol/L respectively for 30 min before ex- posed to cisplatin at 20 mg/L concentrations for 24 h. HMMSCs were treated by U0126 or combined with human epidermal growth factor （HEGF） together for 30 min before they were preconditioned with NariS for 30 min. The cell survival rate, cell apoptosis rate, the expression of p-ERK1/2 and t-ERK1/2 were recorded. Results The cell survival rate decreased to 71.72%±2.72%, 59.41%±5.44%, 50.37%±4.55%, 38.97%±2.92%, 30.11%±4.64% and 21.71%_±5.35% respectively after cells were treated with eisplatin at 5, 10, 20, 40, 60, 80 mg/L concentrations respectively, and the differences were statistically significant compared with 0 mg/L group. The cell viability fell to 70.30%_±6.20%, 61.63%±2.70%, 51.29%_±3.13%, 38.72%±3.66% and 27.57%_±2.32% af- ter HMMSCs were treated with cisplatin at 20 mg/L for 6, 12, 24, 36, 48 h respectively, and the differences were statistically signif- icant compared with 0 h group. The cell viability increased to 65.99%±2.67%, 72.93%_±5.44%, 75.10%±4.71% and 76.56%-± 5.25% when HMMSCs got pretreatment of NariS, and the differences had statistical significance compared with cisplatin group. The cell apoptotic rate decreased from 35.29%±2.77% to 18.62%±0.97% when HMMSCs were pretreated with Naris at 0.6 mmo/ L. Treatment of HMMSCs with cisplatin at 20 mg/L for 24 h reduced p-ERK1/2 expression. The pretreatment of Naris could inhib- it the inhibitory action to the expression of p-ERK1/2 induced by eisplatin. Pretreatment with U0126 or HEGF inhibited or promot- ed the protection and the upregulated expression of p-ERK1/2 caused by NariS pretreatment. Conclusion The preconditioning of H2S can protect cell damage caused by cisplatin via activating the ERKI/2 pathway of HMMSCs. Key words: MAP kinase signaling system;  Hydrogen sulfide;  Mesenchymal stem cells;  Cisplatin;  Cytoproteetion