Radioprotective role of H(2)S/CSE pathway in Chang liver cells

Abstract

Radiation-induced liver cell damage may be life-threatening. Here, we investigated whether hydrogen sulfide (H(2)S)/cystathionine γ-lyase (CSE) pathway could serve the protective role toward radiation in normal human liver cells. Our data showed that pretreatment of cells with H(2)S donor, sodium hydrosulfide (NaHS) significantly attenuated radiation induced micronuclei formation and improved cell viability. However, the use of dl-propargylglycine (PPG), a potent inhibitor of CSE, markedly enhanced the cell-killing effect induced by radiation. Exposure of cells to 2Gy γ-radiation led to significant increases of the endogenous H(2)S content. The mRNA and protein expressions of CSE also increased after radiation in a time-dependent manner, while the expression of cystathionine β-synthase (CBS), another endogenous H(2)S synthetase, did not change significantly. Notably, radiation induced production of reactive oxygen species (ROS) was significantly reversed by the pretreatment of NaHS, while blockage of CSE activity resulted in an enhanced ROS production in irradiated cells. Moreover, NaHS markedly suppressed radiation-induced phosphorylation of P53, decrease of Bcl-2/Bax, and activity of nuclear factor kappaB (NF-κB). In conclusion, our finding demonstrates that H(2)S/CSE pathway plays a radioprotection role by inhibiting radiation-induced ROS production, P53 phosphorylation, NF-κB activation and decrease of Bcl-2/Bax, indicating that modulation of H(2)S may be a novel protection strategy for liver radiation injury in radiotherapy.