UV-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cells. 4. Calcium is involved in the cytotoxicity of UV-treated LDL on lymphoid cell lines.
In lymphoid cells pulsed with 'cytotoxic' concentrations of UV-treated LDL, the study of the variations of free cytosolic calcium concentration, of the influence of extracellular calcium and of the protective effect of calcium chelators suggests that both intra- and extracellular calcium could play a major role in the genesis of cell injury leading to cell death. (1) A dramatic sustained rise of cytosolic free calcium (the level of free cytosolic calcium was higher than 500 nmol/l for 6 h or more) occurred several hours after the beginning of the pulse with UV-treated LDL (lag period between 6 and 12 h). (2) The rise of the free cytosolic calcium and the 'cytotoxicity' induced by UV-treated LDL were largely dependent on the concentration of extracellular calcium which has an effect on the uptake of UV-treated LDL and on the expression of the 'cytotoxicity' at the cellular level. (3) The study of the sequence of intracellular events showed that the cellular oxidative stress generated by oxidized LDL was followed by the rise of free cytosolic calcium and later by the rise of 'cytotoxicity' indexes. (4) The intracellular calcium chelators, BAPTA/AM and EGTA/AM, were able to partially protect lymphoid cells against the 'cytotoxicity' of oxidized LDL. The supposed mechanisms of the free cytosolic calcium rise and the respective role of calcium or/and other factors (for instance direct lesions of the plasma membrane by the oxidative stress due to oxidized LDL) in the genesis of cellular lesions leading to cell death are discussed.
Nègre-Salvayre
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A
Department of Biochemistry, Faculty of Medicine in Rangueil, University Paul Sabatier, Toulouse, France.
Salvayre
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R
D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000633:toxicity*; D016923:Cell Death; D002461:Cell Line, Transformed; D002614:Chelating Agents; D003600:Cytosol / Q000378:metabolism / Q000528:radiation effects; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects; D008054:Lipid Peroxides / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000528:radiation effects / Q000633:toxicity*; D008958:Models, Molecular; D014466:Ultraviolet Rays
D002614:Chelating Agents; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D002118:Calcium