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Titolo:
The bile acid-activated phosphatidylinositol 8-kinase pathway inhibits fasapoptosis upstream of bid in rodent hepatocytes
Autore:
Takikawa, Y; Miyoshi, H; Rust, C; Roberts, P; Siegel, R; Mandal, PK; Millikan, RE; Gores, GJ;
Indirizzi:
Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA Mayo Clin Rochester MN USA iv Gastroenterol & Hepatol, Rochester, MN USA NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA NIAID Bethesda MD USA 20892 AID, Immunol Lab, NIH, Bethesda, MD 20892 USA Univ Texas, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 ourinary Med Oncol, Houston, TX 77030 USA
Titolo Testata:
GASTROENTEROLOGY
fascicolo: 7, volume: 120, anno: 2001,
pagine: 1810 - 1817
SICI:
0016-5085(200106)120:7<1810:TBAP8P>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYTOCHROME-C RELEASE; RAT HEPATOCYTES; CELL-DEATH; SIGNALING COMPLEX; MECHANISM; SURVIVAL; MITOCHONDRIA; CHOLESTASIS; CLEAVAGE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Gores, GJ Mayo Med Sch Clin & Fdn, 200 1st St SW, Rochester, MN 55905 USA Mayo Med Sch Clin & Fdn 200 1st St SW Rochester MN USA 55905 USA
Citazione:
Y. Takikawa et al., "The bile acid-activated phosphatidylinositol 8-kinase pathway inhibits fasapoptosis upstream of bid in rodent hepatocytes", GASTROENTY, 120(7), 2001, pp. 1810-1817

Abstract

<(Background & Aims)>: Bile acids differentially modulate hepatocyte injury in cholestasis, Although glycochenode-oxycholate (GCDC) induces Fas-mediated hepatocyte apoptosis, taurochenodeoxycholate (TCDC) simultaneously activates a phosphatidylinositol 3-kinase (PI 3-K)-mediated survival pathway blocking Fas apoptosis, In this study, the mechanisms by which the TCDC/PI 3-K survival signal disrupts Fas signaling were examined. (Methods) under bar: Studies were performed in primary cultures of mouse hepatocytes and the bile-salt-transporting Mc-Ntcp.24 rat hepatoma cell line. (Results) under bar: GCDC, but not TCDC, resulted in cytochrome c release demonstrating that TCDC blocked apoptosis upstream of mitochondria. In contrast, both GCDC andTCDC treatment resulted in Fas aggregation and recruitment of a dominant-negative FADD green fluorescent protein (GFP) and C360S pro-caspase 8-GFP tothe plasma membrane. Despite recruitment of procaspase 8 to the plasma membrane by both bile acids, only GCDC resulted in increases of caspase 8 activity and Bid-GFP mitochondrial translocation, However, when PI-3K was inhibited with wortmannin or dominant-negative PI 3-K, TCDC-induced Bid-GFP mitochondrial translocation and cytochrome c release. (Conclusions) under bar: The TCDC/PI 3-K survival signal blocks Fas-mediated apoptosis by preventingcaspase 8 activation and Bid mitochondrial translocation, Potentiation of this survival pathway in cholestasis has the potential to attenuate liver injury.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 01:14:02