title: Selenium protects the hypoxia induced apoptosis in neuroblastoma cells through upregulation of Bcl-2.
abstract: Selenium (Se) is an essential micronutrient as well as a toxic trace element in animal and human nutrition. The effects of Se in the immune system and some diseases are well documented. The objective of the present study was to examine the role of Se in reducing the hypoxia induced apoptosis in neuroblastoma cell line. Hypoxia showed an enhanced cytotoxicity, increased free radical production and apoptosis (p<0.001) which was measured in terms of DNA break down by comet assay. Hypoxia has decreased reduced Glutathione (GSH) content, Glutathione Reductase (GR), Glutathione peroxidase (GPx) and Superoxide Dismutase (SOD) activities as compared to control cells. During hypoxic condition the expression of cytochrome C, pro and active caspase-3 levels were enhanced significantly followed by nonsignificant upregulation of Bcl-2. But, the Se supplementation inhibited the cytotoxicity, free radical generation and stabilized the HIF-1alpha accumulation in cells under hypoxia. The GSH content, GR, GPx and SOD activities increased significantly in Se-treated hypoxic cells, as compared to control. Further there was an appreciable inhibition of apoptosis by upregulation of Bcl-2 proteins, in the presence of Se under hypoxia. Selenium supplementation to cells significantly inhibited the hypoxia induced DNA fragmentation and restored the antioxidant status back to control levels. This study suggests that Se supplementation prevented the cells from hypoxia induced apoptosis by triggering upregulation of Bcl-2 protein and reducing the oxidative stress.
authors.affiliation: Department of Experimental Biology, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi-54, India. saradasks@yahoo.com
authors.forename: S K S
authors.initials: SK
authors.lastname: Sarada
authors.forename: P
authors.initials: P
authors.lastname: Himadri
authors.forename: D
authors.initials: D
authors.lastname: Ruma
authors.forename: S K
authors.initials: SK
authors.lastname: Sharma
authors.forename: T
authors.initials: T
authors.lastname: Pauline
authors.lastname: Mrinalini
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009447:Neuroblastoma; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects* / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000975:Antioxidants; D005609:Free Radicals; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D013482:Superoxide Dismutase; D005978:Glutathione; D012643:Selenium