Protective Effect of Reduced Glutathione C_(60) Derivative against Hydrogen Peroxide-induced Apoptosis in HEK 293T Cells

摘要

Hydrogen peroxide(H_2O_2) and free radicals cause oxidative stress, which induces cellular injuries, metabolic dysfunction, and even cell death in various clinical abnormalities. Fullerene(C_(60)) is critical for scavenging oxygen free radicals originated from cell metabolism, and reduced glutathione(GSH) is another important endogenous antioxidant. In this study, a novel water-soluble reduced glutathione fullerene derivative(C_(60)-GSH) was successfully synthesized, and its beneficial roles in protecting against H_2O_2-induced oxidative stress and apoptosis in cultured HEK 293 T cells were investigated. Fourier Transform infrared spectroscopy and 1H nuclear magnetic resonance were used to confirm the chemical structure of C_(60)-GSH. Our results demonstrated that C_(60)-GSH prevented the reactive oxygen species(ROS)-mediated cell damage. Additionally, C_(60)-GSH pretreatment significantly attenuated H_2O_2-induced superoxide dismutase(SOD) consumption and malondialdehyde(MDA) elevation. Furthermore, C_(60)-GSH inhibited intracellular calcium mobilization, and subsequent cell apoptosis via bcl-2/bax-caspase-3 signaling pathway induced by H_2O_2 stimulation in HEK 293 T cells. Importantly, these protective effects of C_(60)-GSH were superior to those of GSH. In conclusion, these results suggested that C_(60)-GSH has potential to protect against H_2O_2-induced cell apoptosis by scavenging free radicals and maintaining intracellular calcium homeostasis without evident toxicity.