Fas-induced apoptosis in mouse hepatocytes is dependent on C/EBPbeta

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
D MukherjeeL Greenbaum

Abstract

Apoptotic cell death in the liver in response to activation of the Fas pathway has been implicated in human disease states as well as liver remodeling and tissue repair. C/EBPbeta, a member of the CCAAT enhancer binding protein family of bZIP transcription factors has been linked to both growth response and apoptotic targets in the liver, and, therefore, is a likely candidate for the regulation of apoptotic liver injury. We investigated differences in apoptotic cell death in the livers of C/EBPbeta-null mice using the Jo-2 agonistic anti-Fas antibody. Apoptotic injury was dramatically reduced in C/EBPbeta -/- livers as shown by a nearly 20-fold reduction in apoptotic hepatocytes 6 hours post-Jo-2 treatment in C/EBPbeta -/- hepatocytes compared with controls (P < .04) and reduced activation of caspase 3. Bid cleavage occurred in Jo-2 treated C/EBPbeta -/- livers indicating a block of Fas-induced injury distal to the death-inducing signaling complex. The level of the antiapoptotic protein bcl-x(L) was increased greater than tenfold in the mutant animals (P < .04), which can, at least in part, account for the protection from Fas-mediated apoptosis. In contrast, bcl-x(L) mRNA levels were unchanged. These observations link C/EBPbeta...Continue Reading

Citations

Jul 1, 2009·Journal of Molecular Biology·Xiaorong LiCheng Cao
Jan 22, 2005·Clinical Transplantation·Tokihiko SawadaSatoshi Teraoka
Sep 16, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tom LueddeChristian Trautwein
Oct 28, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yongjun WangMark J Czaja

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