title: Calcium ions and oxidative cell injury.
abstract: Exposure of mammalian cells to oxidative stress induced by oxidation-reduction-active quinones and other prooxidants results in depletion of intracellular glutathione, followed by modification of protein thiols and loss of cell viability. Protein thiol modification during oxidative stress is normally associated with impairment of various cell functions, including inhibition of agonist-stimulated phosphoinositide metabolism, disruption of intracellular Ca2+ homeostasis, and perturbation of normal cytoskeletal organization. The latter effect appears to be responsible for formation of the numerous plasma membrane blebs typically seen in cells exposed to cytotoxic concentrations of prooxidants. Following disruption of thiol homeostasis in prooxidant-treated cells, there is impairment of Ca2+ transport and subsequent perturbation of intracellular Ca2+ homeostasis, resulting in a sustained increase in cytosolic Ca2+ concentration. This increase in Ca2+ can cause activation of various Ca(2+)-dependent degradative enzymes (e.g., phospholipases, proteases, endonucleases), which may contribute to cell death. In contrast to the cytotoxic effects of excessive oxidative damage, low levels of oxidative stress can lead to activation of enzymes involved in cell signaling. In particular, the activity of protein kinase C is markedly increased by oxidation-reduction-cycling quinones through a thiol/disulfide exchange mechanism, which may represent a mechanism by which prooxidants can modulate cell growth and differentiation.
authors.affiliation: Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Orrenius
authors.forename: M J
authors.initials: MJ
authors.lastname: Burkitt
authors.forename: G E
authors.initials: GE
authors.lastname: Kass
authors.forename: J M
authors.initials: JM
authors.lastname: Dypbukt
authors.forename: P
authors.initials: P
authors.lastname: Nicotera
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D006801:Humans; D010084:Oxidation-Reduction
chemical_list: D002118:Calcium