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Titolo:
Tributyltin interacts with mitochondria and induces cytochrome c release
Autore:
Nishikimi, A; Kira, Y; Kasahara, E; Sato, EF; Kanno, T; Utsumi, K; Inoue, M;
Indirizzi:
Osaka City Univ, Sch Med, Dept Biochem & Mol Pathol, Osaka 5458585, Japan Osaka City Univ Osaka Japan 5458585 m & Mol Pathol, Osaka 5458585, Japan Kurashiki Med Ctr, Inst Med Sci, Kurashiki, Okayama 7108522, Japan Kurashiki Med Ctr Kurashiki Okayama Japan 7108522 Okayama 7108522, Japan
Titolo Testata:
BIOCHEMICAL JOURNAL
, volume: 356, anno: 2001,
parte:, 2
pagine: 621 - 626
SICI:
0264-6021(20010601)356:<621:TIWMAI>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERMEABILITY TRANSITION PORE; RAT-LIVER MITOCHONDRIA; ORGANOTIN COMPOUNDS; NONSPECIFIC RESISTANCE; TRIETHYLTIN BROMIDE; ADP/ATP CARRIER; CAT HEMOGLOBIN; ANION CHANNEL; TERM EXPOSURE; APOPTOSIS;
Keywords:
adenine nucleotide translocator; apoptosis; permeability transition; swelling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Inoue, M Osaka City Univ, Sch Med, Dept Biochem & Mol Pathol, Osaka 5458585, Japan Osaka City Univ Osaka Japan 5458585 athol, Osaka 5458585, Japan
Citazione:
A. Nishikimi et al., "Tributyltin interacts with mitochondria and induces cytochrome c release", BIOCHEM J, 356, 2001, pp. 621-626

Abstract

Although triorganotins are potent inducers of apoptosis in various cell types, the critical targets of these compounds and the mechanisms by which they lead to cell death remain to be elucidated. There are two major pathwaysby which apoptotic cell death occurs: one is triggered by a cytokine mediator and the other is by a mitochondrion-dependent mechanism. To elucidate the mechanism of triorganotin-induced apoptosis, we studied the effect of tributyltin on mitochondrial function. We found that moderately low doses of tributyltin decrease mitochondrial membrane potential and induce cytochromec release by a mechanism inhibited by cyclosporine A and bongkrekic acid. Tributyltin-induced cytochrome c release is also prevented by dithiols suchas dithiothreitol and 2,3-dimercaptopropanol but not by monothiols such asGSH, N-acetyl-L-cysteine, L-cysteine and 2-mercaptoethanol. Further studies with phenylarsine oxide agarose revealed that tributyltin interacts with the adenine nucleotide translocator, a functional constituent of the mitochondrial permeability transition pore, which is selectively inhibited by dithiothreitol. These results suggest that, at low doses, tributyltin interacts selectively with critical thiol residues in the adenine nucleotide translocator and opens the permeability transition pore, thereby decreasing membrane potential and releasing cytochrome c from mitochondria, a series of events consistent with established mechanistic models of apoptosis.

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Documento generato il 14/07/20 alle ore 09:18:23