title: Protective effect of reduced glutathione C60 derivative against hydrogen peroxide-induced apoptosis in HEK 293T cells.
abstract: Hydrogen peroxide (H2O2) and free radicals cause oxidative stress, which induces cellular injuries, metabolic dysfunction, and even cell death in various clinical abnormalities. Fullerene (C60) 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 (C60-GSH) was successfully synthesized, and its beneficial roles in protecting against H2O2-induced oxidative stress and apoptosis in cultured HEK 293T cells were investigated. Fourier Transform infrared spectroscopy and (1)H nuclear magnetic resonance were used to confirm the chemical structure of C60-GSH. Our results demonstrated that C60-GSH prevented the reactive oxygen species (ROS)-mediated cell damage. Additionally, C60-GSH pretreatment significantly attenuated H2O2-induced superoxide dismutase (SOD) consumption and malondialdehyde (MDA) elevation. Furthermore, C60-GSH inhibited intracellular calcium mobilization, and subsequent cell apoptosis via bcl-2/bax-caspase-3 signaling pathway induced by H2O2 stimulation in HEK 293T cells. Importantly, these protective effects of C60-GSH were superior to those of GSH. In conclusion, these results suggested that C60-GSH has potential to protect against H2O2-induced cell apoptosis by scavenging free radicals and maintaining intracellular calcium homeostasis without evident toxicity.
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Guan
authors.affiliation: Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. liushtj@yahoo.com.cn.
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Liu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008315:Malondialdehyde / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; C494826:BAX protein, human; C000595707:BCL2 protein, human; D037741:Fullerenes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; C505407:CASP3 protein, human; D053148:Caspase 3; D005978:Glutathione; C069837:fullerene C60; D002118:Calcium
keywords: HEK 293T cells; apoptosis; hydrogen peroxide; oxidative stress; reduced glutathione C60 derivative