Protective effect of reduced glutathione C sub(60) derivative against hydrogen peroxide-induced apoptosis in HEK 293T cells

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences 2016-06, Vol.36 (3), p.356-363
• Main Authors: Huang, Jin, Zhou, Chi, He, Jun, Hu, Zheng, Guan, Wen-chao, Liu, Sheng-hong
• Format: Article
• Language: English
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-016-1591-x

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