title: Cell calcium, vitamin E, and the thiol redox system in cytotoxicity.
abstract: The controversial role of extracellular Ca2+ in toxicity to in vitro hepatocyte systems is reviewed. Recent reports demonstrate that extracellular Ca2+-related cytotoxicity is dependent on Ca2+-influenced vitamin E (alpha-tocopherol) content of isolated hepatocytes. Based on a Ca2+-omission model of in vitro oxidative stress, the role of vitamin E in cytotoxicity is further explored. This model demonstrates the interdependence of the GSH redox system and vitamin E as protective agents during oxidative stress. Following chemical oxidant-induced depletion of intracellular GSH, cell morphology and viability are maintained by the continuous presence of cellular alpha-tocopherol above a threshold level of 0.6-1.0 nmol/10(6) cells. alpha-Tocopherol threshold-dependent cell viability is directly correlated with the prevention of the loss of cellular protein thiols in the absence of intracellular GSH. Potential mechanisms for this phenomenon are explored and include a direct reductive action of alpha-tocopherol on protein thiyl radicals, and the prevention of oxidation of protein thiols by scavenging of lipid peroxyl radicals by alpha-tocopherol. It is suggested that in light of the threshold phenomenon of vitamin E prevention of potentially severe oxidative stress-induced cytotoxicity, its use as a protective agent against an oxidative challenge in vivo should be reassessed.
authors.affiliation: Environmental Health Sciences Center, Oregon State University, Corvallis 97331.
authors.forename: G A
authors.initials: GA
authors.lastname: Pascoe
authors.forename: D J
authors.initials: DJ
authors.lastname: Reed
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D005978:Glutathione / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014810:Vitamin E / Q000502:physiology*
chemical_list: D013438:Sulfhydryl Compounds; D014810:Vitamin E; D005978:Glutathione; D002118:Calcium