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Titolo:
Mitochondrial permeability transition induced by the anticancer drug etoposide
Autore:
Custodio, JBA; Cardoso, CMP; Madeira, VMC; Almeida, LM;
Indirizzi:
Univ Coimbra, Fac Farm, Lab Bioquim, Coimbra, Portugal Univ Coimbra Coimbra Portugal Fac Farm, Lab Bioquim, Coimbra, Portugal Univ Coimbra, Ctr Neurociencia, Coimbra, Portugal Univ Coimbra Coimbra Portugal mbra, Ctr Neurociencia, Coimbra, Portugal
Titolo Testata:
TOXICOLOGY IN VITRO
fascicolo: 4-5, volume: 15, anno: 2001,
pagine: 265 - 270
SICI:
0887-2333(200108/10)15:4-5<265:MPTIBT>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYTOCHROME-C; CELL-DEATH; INDUCED APOPTOSIS; INDUCTION; MEMBRANE; RELEASE; PHOSPHORYLATION; GLUTATHIONE; ACTIVATION; INHIBITORS;
Keywords:
etoposide; anticancer; apoptosis; liver mitochondria; mitochondrial permeability transition;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Custodio, JBA Univ Coimbra, Fac Farm, Lab Bioquim, Coimbra, Portugal Univ Coimbra Coimbra Portugal Bioquim, Coimbra, Portugal
Citazione:
J.B.A. Custodio et al., "Mitochondrial permeability transition induced by the anticancer drug etoposide", TOX VITRO, 15(4-5), 2001, pp. 265-270

Abstract

Etoposide (VP-16) is widely used for the treatment of several forms of cancer. The cytotoxicity of VP-16 has been assigned to the induction of apoptotic cell death but the signaling pathway for VP-16-induced apoptosis is essentially unknown. There is some evidence that this process depends on events associated with the loss of mitochondrial membrane potential (Delta Psi) and/or release of apoptogenic factors, putatively as a consequence of mitochondrial permeability transition (MPT) induction. This work evaluates the interference of VP-16 with MPT in vitro, which is characterized by the Ca2+-dependent depolarization of Atp, the release of matrix Ca2+ and by extensive swelling of mitochondria. Delta Psi depolarization and Ca2+ release were measured with ion-selective electrodes, and mitochondrial swelling was monitored spectrophotometrically. Incubation of rat liver mitochondria with VP-16 results in a concentration-dependent induction of MPT, evidenced by an increased sensitivity to Ca2+-induced swelling, depolarization of Delta Psi,Ca2+ release by mitochondria and stimulation of state 4 oxygen consumption. All of these effects are prevented by preincubating the mitochondria withcyclosporine A, a potent and specific inhibitor of the MPT. Therefore, VP-16 increases the sensitivity of isolated mitochondria to the Ca2+-dependentinduction of the MPT. Together, these data provide a possible mechanistic explanation for the previously reported effects of VP-16 on apoptosis induction. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 18:19:13