Intracellular calcium chelators and oxidant-induced renal proximal tubule cell death.
The effect of intracellular calcium chelators on rabbit renal proximal tubule (RPT) cell death induced by t-butyl hydroperoxide (TBHP) and H2O2 was examined. Preincubation of RPT suspensions with 50 microM QUIN 2/AM completely prevented TBHP (0.5 mM) and H2O2 (2 mM) induced cell death [i.e., release of lactate dehydrogenase (LDH)]. QUIN 2/AM, BAPTA/AM, EGTA/AM, and FURA 2/AM, at 5 microM, decreased LDH release (at 6 hr) from 41% to 4%, 21%, 26%, and 33%, and decreased lipid peroxidation (at 1 hr) from 1.0 to 0.1, 0.4, 0.6, and 0.8 nmol MDA/mg protein, respectively, after TBHP exposure. Since oxidant-induced lipid peroxidation and cell death are iron-dependent in this model, these results suggest that the intracellular calcium chelators inhibit cell death by chelating iron.
Schnellmann
R G
RG
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602.
D000634:Aminoquinolines / Q000633:toxicity; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002614:Chelating Agents / Q000633:toxicity*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D016257:Fura-2 / Q000633:toxicity; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects*; D011817:Rabbits
D000634:Aminoquinolines; D002614:Chelating Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D007501:Iron; C035739:Quin2; D002118:Calcium; D016257:Fura-2