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Titolo:
Hepatocyte growth factor promotes renal epithelial cell survival by dual mechanisms
Autore:
Liu, YH;
Indirizzi:
Brown Univ, Rhode Isl Hosp, Sch Med, Dept Med, Providence, RI 02903 USA Brown Univ Providence RI USA 02903 ed, Dept Med, Providence, RI 02903 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
fascicolo: 4, volume: 277, anno: 1999,
pagine: F624 - F633
SICI:
0363-6127(199910)277:4<F624:HGFPRE>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
C-MET; PHOSPHATIDYLINOSITOL 3-KINASE; PROTOONCOGENE PRODUCT; BLOCKS APOPTOSIS; FACTOR RECEPTOR; FACTOR-I; DEATH; SCATTER; AKT; HGF;
Keywords:
c-met; apoptosis; Bad; Bcl-xL; phosphorylation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Liu, YH Univ Pittsburgh, Sch Med, Dept Pathol, S-428 Biomed Sci Tower, Pittsburgh,PA 15261 USA Univ Pittsburgh S-428 Biomed Sci Tower Pittsburgh PA USA 15261 USA
Citazione:
Y.H. Liu, "Hepatocyte growth factor promotes renal epithelial cell survival by dual mechanisms", AM J P-REN, 277(4), 1999, pp. F624-F633

Abstract

Hepatocyte growth factor (HGF) has been shown to protect renal epithelial cells against apoptosis. To define the mechanism by which HGF inhibits apoptosis, we investigated the effect of HGF on the phosphorylation and expression of the Bcl-2 family proteins. Using a human proximal tubular epithelialcell (HKC) line as a model, ave demonstrated that constitutive expression of HGF conveyed marked resistance to apoptotic death induced by serum withdrawal. HGF induced rapid phosphorylation of Akt in HKC cells, which was immediately followed by phosphorylation and resultant inactivation of Bad, a pro-apoptotic member of the Bcl-2 family. Pretreatment of the HKC cells with10 nM wortmannin completely abolished HGF-induced phosphorylation of Akt and Bad, suggesting that this pathway is dependent on phosphoinositide (PT) 3-kinase. Overexpression of Bad increased apoptotic death in wild-type HKC cells but not in HGF-producing H4 cells. Immunoblotting confirmed that the Bad protein overexpressed in H4 cells was fully phosphorylated at both Ser(112) and Ser(136) sites. Prolonged incubation of HKC cells with HGF also dramatically induced expression of Bcl-xL, an anti-apoptotic member of the Bcl-2 family. These results suggest that the anti-apoptotic effect of HGF in renal epithelial cells is mediated by dual mechanisms involving two distinct Bcl-2 family proteins. HGF triggers Bad phosphorylation via the PI 3-kinase/Akt pathway, thereby inactivating this pro-apoptotic protein, while simultaneously inducing expression of anti-apoptotic 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 10:30:21