title: beta-sitosterol decreases irradiation-induced thymocyte early damage by regulation of the intracellular redox balance and maintenance of mitochondrial membrane stability.
abstract: Both radiation injury and oxidation toxicity occur when cells are exposed to ion irradiation (IR), ultimately leading to apoptosis. This study was designed to determine the effect of beta-sitosterol (BSS) on early cellular damage in irradiated thymocytes and a possible mechanism of effect on irradiation-mediated activation of the apoptotic pathways. Thymocytes were irradiated (6 Gy) with or without BSS. Cell apoptosis and apoptosis-related proteins were evaluated. BSS decreased irradiation-induced cell death and nuclear DNA strand breaks while attenuating intracellular reactive oxygen species (ROS) and increasing the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). BSS decreased the release of cytochrome c from mitochondria to the cytosol and the mitochondrio-nuclear translocation of apoptosis-inducing factor (AIF). Furthermore, BSS partially inhibited the radiation-induced increase of cleaved caspase 3 and cleaved PARP, and attenuated the activation of JNK and AP-1. In addition, evidence suggests that ROS generated by irradiation are involved in this course of cell damage. The results indicate that BSS confers a radioprotective effect on thymocytes by regulation of the intracellular redox balance which is carried out via the scavenging of ROS and maintenance of mitochondrial membrane stability.
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Taiping Road 27#, Haidian district, Beijing 100850, People's Republic of China.
authors.forename: Chun Rong
authors.initials: CR
authors.lastname: Li
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou
authors.forename: Ru Xin
authors.initials: RX
authors.lastname: Lin
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.forename: Yu Ning
authors.initials: YN
authors.lastname: Sun
authors.forename: Lin Lin
authors.initials: LL
authors.lastname: Tian
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.forename: Sheng Qi
authors.initials: SQ
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D015398:Signal Transduction; D012855:Sitosterols / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
chemical_list: D051033:Apoptosis Inducing Factor; D000960:Hypolipidemic Agents; D012855:Sitosterols; C025473:gamma-sitosterol; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase