Involvement of P2Y receptors in the protective effect of ATP towards the cell damage in HaCaT cells exposed to H2O2

It has recently been reported that activation of P2Y(1) receptor, one of the purine receptors, by extracellular nucleotides induces cytoprotection against oxidative stress. In this study, we examined the protective effect of ATP on the cell damage in human epidermal keratinocyte HaCaT cells exposed to H2O2 via the P2Y receptor-mediated induction of intracellular antioxidants. The cells were damaged by exposure to H2O2 in a dose- and time-dependent manner. The damage induced by 7.5 mM H2O2 was blocked by pretreatment of the cells with ATP (1-10 mu M). The protective effect of ATP was significantly reduced by P2Y receptor antagonists. Exogenously added ATP induced various intracellular antioxidants, including thiol-containing proteins, Cu/Zn superoxide dismutase (SOD) and thioredoxin-1, in HaCaT cells. In conclusion, it was found that ATP protected the cells from the H2O2-induced cell damages via the P2Y receptor-mediated induction of intracellular antioxidants.