High susceptibility of activated lymphocytes to oxidative stress-induced cell death.
The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH)-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.
Degasperi
Giovanna R
GR
Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.
Castilho
Roger F
RF
Vercesi
Anibal E
AE
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002279:Carcinoma 256, Walker; D002614:Chelating Agents / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017262:Siderophores / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
D002614:Chelating Agents; D017262:Siderophores; D004533:Egtazic Acid; D020122:tert-Butylhydroperoxide; D009543:Nifedipine; D003676:Deferoxamine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium