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Titolo:
Akt protects mouse hepatocytes from TNF-alpha- and Fas-mediated apoptosis through NK-kappa B activation
Autore:
Hatano, E; Brenner, DA;
Indirizzi:
Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 t Med, Chapel Hill, NC 27599 USA Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 ophys, Chapel Hill, NC 27599 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
fascicolo: 6, volume: 281, anno: 2001,
pagine: G1357 - G1368
SICI:
0193-1857(200112)281:6<G1357:APMHFT>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; EPIDERMAL GROWTH-FACTOR; MITOCHONDRIAL PERMEABILITY TRANSITION; SEVERE LIVER DEGENERATION; KINASE-B; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; PHOSPHOINOSITIDE 3-KINASE; GENE-TRANSCRIPTION; DEFICIENT MICE; DEATH FACTOR;
Keywords:
Bcl-xL; phosphatidylinositol 3-kinase; I kappa B kinase; transcription; signaling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Brenner, DA Univ N Carolina, Dept Med, CB 7038,156 Glaxo, Chapel Hill, NC 27599 USA Univ N Carolina CB 7038,156 Glaxo Chapel Hill NC USA 27599 USA
Citazione:
E. Hatano e D.A. Brenner, "Akt protects mouse hepatocytes from TNF-alpha- and Fas-mediated apoptosis through NK-kappa B activation", AM J P-GAST, 281(6), 2001, pp. G1357-G1368

Abstract

To determine the role of phosphatidylinositol 3-kinase (PI3K)/Akt and nuclear factor- kappaB (NF-kappaB) in protecting hepatocytes from tumor necrosis factor-alpha (TNF-alpha)- and Fas-mediated apoptosis, we pretreated primary cultures of mouse hepatocytes with pharmacological and adenovirus-mediated inhibitors of the PI3K/Akt and NF-kappaB pathways followed by treatment with TNF-alpha or Jo2, an anti-Fas antibody. Jo2 and, to a lesser extent, TNF-alpha phosphorylate Akt. The PI3K inhibitor LY-294002 blocks TNF-alpha- and Fas-mediated Akt phosphorylation. LY-294002 pretreatment reduces NF-kappaB binding activity and transcriptional activity and NF-kappaB-responsive gene expression by TNF-alpha or Jo2. LY-294002 promotes apoptosis after TNF-alpha or Jo2. The expression of dominant-negative Akt blocks NF-kappaB activation and sensitizes hepatocytes to TNF-alpha- and Fas-mediated apoptosis. The expression of constitutively active Akt rescues LY-294002-pretreated cells from TNF-alpha- and Fas-mediated apoptosis. Active Akt induces NF-kappaB transcriptional activity but not NF-kappaB binding activity or I kappaBdegradation. Furthermore, LY-294002 pretreatment blocks TNF-alpha- and Jo2-induced Bcl-xL levels in hepatocytes, with no effect on the phosphorylation levels of Bad. Bcl-xL overexpression protects hepatocytes from Fas-but not TNF-alpha -induced apoptosis after sensitization by actinomycin D or the I kappaB superrepressor. Together, the PI3K/Akt pathway has a protective role in Fas-mediated apoptosis, which requires NF-kappaB activation, partially through the subsequent induction of Bcl-xL.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 11:21:03