Effect of hydrogen sulfide on PC12 cell injury induced by high ATP concentration

Abstract

Purpose: To investigate the potential protective effect of hydrogen sulfide against neural cell damage induced by a high-concentration of adenosine triphosphate (ATP).Methods: PC12 cells were incubated with ATP in order to induce cell damage. The extracellular level of H2S and protein expression of cystathionine-β-synthase (CBS) were determined. The PC12 cells pretreated with NaHS, aminooxyacetic acid (AOAA) and KN-62, prior to further incubation with ATP, and the effect of the treatments on cell viability was investigated.Results: High-concentration ATP induced cell death in PC12 cells, and this was accompanied by markedly increased contents of extracellular H2S and CBS expression (p < 0.05). The ATP-induced cytotoxicity was significantly compromised after pretreatment with H2S. (p < 0.05). The viability of PC12 cells pretreated with NaHS and AOAA was significantly higher than that of PC12 cells treated with ATP alone. In addition, the viability of ATP-treated PC12 cells was further markedly increased after pretreatment with NaHS and KN-62 (p < 0.05).Conclusion: ATP induced a concentration- and time-dependent cytotoxicity in PC12 cells via theendogenous H2S/CBS system. Supplementation with exogenous H2S mitigated the cell damageinduced by high concentration of ATP via a specific mechanism which may be specifically related to P2X7R.