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Titolo:
Regulation of tumor necrosis factor cytotoxicity by calcineurin
Autore:
Kantrow, SP; Gierman, JL; Jaligam, VR; Zhang, P; Piantadosi, CA; Summer, WR; Lancaster, JR;
Indirizzi:
Louisiana State Univ, Hlth Sci Ctr, Dept Med, New Orleans, LA 70112 USA Louisiana State Univ New Orleans LA USA 70112 , New Orleans, LA 70112 USA Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA Louisiana State Univ New Orleans LA USA 70112 , New Orleans, LA 70112 USA Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 iv, Med Ctr, Dept Med, Durham, NC 27710 USA
Titolo Testata:
FEBS LETTERS
fascicolo: 2-3, volume: 483, anno: 2000,
pagine: 119 - 124
SICI:
0014-5793(20001020)483:2-3<119:ROTNFC>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
MITOCHONDRIAL PERMEABILITY TRANSITION; T-CELL HYBRIDOMAS; CYCLOSPORINE-A; CYTOCHROME-C; PHOSPHATASE-ACTIVITY; APOPTOSIS; DEATH; RELEASE; ACTIVATION; THYMOCYTES;
Keywords:
calcineurin; apoptosis; mitochondrion; cytochrome c; cyclosporin A; FK506;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Kantrow, SP Louisiana State Univ, Hlth Sci Ctr, Dept Med, 1901 Perdido St,Suite 3205, New Orleans, LA 70112 USA Louisiana State Univ 1901 Perdido St,Suite 3205 New Orleans LA USA 70112
Citazione:
S.P. Kantrow et al., "Regulation of tumor necrosis factor cytotoxicity by calcineurin", FEBS LETTER, 483(2-3), 2000, pp. 119-124

Abstract

Cyclosporin (CsA) inhibits mitochondrial death signaling and opposes tumornecrosis factor (TNF)-induced apoptosis in vitro. However, CsA is also a potent inhibitor of calcineurin, a phosphatase that may participate in cell death. Therefore, we tested the hypothesis that calcineurin regulates TNF cytotoxicity in rat hepatoma cells (FTO2B), TNF-treated FTO2B cells appearedapoptotic by DNA fragmentation, nuclear condensation, annexin V binding, and caspase activation. We studied two calcineurin inhibitors, CsA and FK506, and found that each potently inhibited TNF cytotoxicity, Western blot demonstrated calcineurin in FTO2B homogenates. In a model of mitochondrial permeability transition (MPT), we found that CsA prevented MPT and cytochrome c release, while FK506 inhibited neither. In summary, we present evidence that calcineurin participates in an apoptotic death pathway activated by TNF, CsA may oppose programmed cell death by inhibiting calcineurin activity and/or inhibiting mitochondrial signaling. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

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Documento generato il 16/07/20 alle ore 19:55:28