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Titolo:
Epidermal growth factor impairs the cytochrome C/caspase-3 apoptotic pathway induced by transforming growth factor beta in rat fetal hepatocytes via a phosphoinositide 3-kinase-dependent pathway
Autore:
Fabregat, I; Herrera, B; Fernandez, M; Alvarez, AM; Sanchez, A; Roncero, C; Ventura, JJ; Valverde, AM; Benito, M;
Indirizzi:
Univ Complutense Madrid, Fac Farm, CSIC, Dept Bioquim & Biol Mol,Ctr Mixto, E-28040 Madrid, Spain Univ Complutense Madrid Madrid Spain E-28040 ixto, E-28040 Madrid, Spain Univ Complutense Madrid, Ctr Citometria Flujo & Microscopia Coniocal, E-28040 Madrid, Spain Univ Complutense Madrid Madrid Spain E-28040 ocal, E-28040 Madrid, Spain
Titolo Testata:
HEPATOLOGY
fascicolo: 3, volume: 32, anno: 2000,
pagine: 528 - 535
SICI:
0270-9139(200009)32:3<528:EGFITC>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
PRIMARY CULTURE; EPITHELIAL-CELLS; HEPATOMA-CELLS; C RELEASE; BCL-XL; MITOCHONDRIA; DEATH; LIVER; INDUCTION; BAX;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Fabregat, I Univ Complutense Madrid, Fac Farm, CSIC, Dept Bioquim & Biol Mol,Ctr Mixto, Ciudad Univ, E-28040 Madrid, Spain Univ Complutense Madrid Ciudad Univ Madrid Spain E-28040 pain
Citazione:
I. Fabregat et al., "Epidermal growth factor impairs the cytochrome C/caspase-3 apoptotic pathway induced by transforming growth factor beta in rat fetal hepatocytes via a phosphoinositide 3-kinase-dependent pathway", HEPATOLOGY, 32(3), 2000, pp. 528-535

Abstract

Transforming growth factor beta (TGF-beta)-mediated apoptosis is one of the major death processes in the liver. We have previously shown that epidermal growth factor (EGF) is an important survival signal for TGF-beta-inducedapoptosis in fetal hepatocytes (Fabregat et al., FEES Lett 1996;384:14-18). In this work we have studied the intracellular signaling implicated in the protective effect of EGF, We show here that EGF activates p42 and p44 mitogen-activated protein kinases (MAPK). However, mitogen extracellular kinase (MEK) inhibitors do not block the survival effect of EGF. EGF also activates phosphoinositide 3-kinase (PI 3-kinase) and protein kinase B (PKB/AKT) in these cells. The presence of PI 3-kinase inhibitors blocks the protective effect of EGF on cell viability, DNA fragmentation, and caspase-3 activity. We have found that TGF-beta disrupts the mitochondrial transmembrane potential (Delta Psi(m)) and activates the release of cytochrome c, this effect being blocked by EGF, via a PI 3-kinase-dependent pathway. A detailed study on bcl-2 superfamily gene expression shows that TGF-beta produces a decrease in the messenger RNA (mRNA) and protein levels of bcl-x(L), an antiapoptotic member of this family, capable of preventing cytochrome c release. EGF is able to maintain bcl-x(L) levels even in the presence of TGF-beta. PI3-kinase inhibitors completely block the protective effect of EGF on TGF-beta-induced bcl-xL down-regulation. We conclude that PI 3-kinase mediates the survival effect of EGF on TGF-beta-induced death by acting upstream fromthe mitochondrial changes, i.e., preventing bcl-x(L) down-regulation, cytochrome c release, and activation of caspase-3.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 14:08:11