title: The operation of Na+/Ca2+ exchanger prevents intracellular Ca2+ overload and hepatocyte killing following iron-induced lipid peroxidation.
abstract: Stimulation of lipid peroxidation by incubating isolated rat hepatocytes with ADP/FeCl3 caused a time dependent increase in cytosolic free Ca2+ levels, without influencing cellular Na+ content. Omission of Na+ from the incubation medium greatly increased the accumulation of Ca2+, which was partially reverted upon transferring the cells in a Na+ containing medium. This suggested that a Na(+)-dependent Ca2+ transporter was activated upon the elevation of cytosolic Ca2+ and partially counteracted the influx of Ca2+ promoted by lipid peroxidation. In the presence of Na+ cell death was not associated with the increase of Ca2+ induced by peroxidative injury; however, decrease of mitochondrial membrane potential and loss of cell viability followed by massive accumulation of Ca2+ occurring in hepatocytes incubated with ADP/FeCl3 in a Na(+)-free medium. Both these effects were completely prevented by chelation of extracellular Ca2+ with EGTA. Thus, we conclude that Na(+)-dependent Ca2+ transporter is involved in controlling excessive accumulation of Ca2+ induced by stimulation of lipid peroxidation and can prevent hepatocyte death caused by Ca(2+)-dependent alterations of mitochondrial activity.
authors.affiliation: Dept. of Medical Sciences, University of Torino, Novara, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Carini
authors.forename: G
authors.initials: G
authors.lastname: Bellomo
authors.forename: M U
authors.initials: MU
authors.lastname: Dianzani
authors.forename: E
authors.initials: E
authors.lastname: Albano
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002470:Cell Survival; D066298:In Vitro Techniques; D007501:Iron / Q000633:toxicity; D008054:Lipid Peroxides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D051381:Rats; D019831:Sodium-Calcium Exchanger
chemical_list: D002352:Carrier Proteins; D008054:Lipid Peroxides; D019831:Sodium-Calcium Exchanger; D007501:Iron; D002118:Calcium