Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice
- PMID: 8564847
- DOI: 10.1038/nm0196-80
Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice
Abstract
Fas is an apoptosis-signalling cell surface antigen that has been shown to trigger cell death upon specific ligand or antibody binding. Treatment of mice with an anti-Fas antibody causes fulminant hepatic failure due to massive apoptosis. To test a putative protective effect of the anti-apoptotic Bcl-2 protein, transgenic mice were generated to express the human bcl-2 gene product in hepatocytes. Early onset of massive hepatic apoptosis leading to death was observed in all nontransgenic mice treated with an anti-Fas antibody. By contrast, hepatic apoptosis was delayed and dramatically reduced in transgenic animals, yielding a 93% survival rate. These results demonstrate that Bcl-2 is able to protect from in vivo Fas-mediated cytotoxicity, and could be of significance for preventing fulminant hepatic failure due to viral hepatitis in humans.
Similar articles
-
A bcl-2 transgene expressed in hepatocytes protects mice from fulminant liver destruction but not from rapid death induced by anti-Fas antibody injection.J Exp Med. 1996 Mar 1;183(3):1031-6. doi: 10.1084/jem.183.3.1031. J Exp Med. 1996. PMID: 8642244 Free PMC article.
-
Transforming growth factor alpha protects against Fas-mediated liver apoptosis in mice.FEBS Lett. 2002 May 22;519(1-3):11-5. doi: 10.1016/s0014-5793(02)02677-7. FEBS Lett. 2002. PMID: 12023010
-
Differential protective effects of Bcl-xL and Bcl-2 on apoptotic liver injury in transgenic mice.Am J Physiol. 1999 Sep;277(3):G702-8. doi: 10.1152/ajpgi.1999.277.3.G702. Am J Physiol. 1999. PMID: 10484397
-
[Involvement of Fas and Fas ligand in case of human fulminant hepatitis].Nihon Rinsho. 1996 Jul;54(7):1965-9. Nihon Rinsho. 1996. PMID: 8741696 Review. Japanese.
-
Mutations in apoptosis genes: a pathogenetic factor for human disease.Mutat Res. 2001 Jul;488(3):211-31. doi: 10.1016/s1383-5742(01)00057-6. Mutat Res. 2001. PMID: 11397650 Review.
Cited by
-
The nude mouse as model for liver deficiency study and treatment and xenotransplantation.Int J Hepatol. 2012;2012:140147. doi: 10.1155/2012/140147. Epub 2012 Oct 31. Int J Hepatol. 2012. PMID: 23193481 Free PMC article.
-
A novel in vivo siRNA delivery system specifically targeting liver cells for protection of ConA-induced fulminant hepatitis.PLoS One. 2012;7(9):e44138. doi: 10.1371/journal.pone.0044138. Epub 2012 Sep 6. PLoS One. 2012. PMID: 22970170 Free PMC article.
-
Cross-talk in cell death signaling.J Exp Med. 2000 Oct 16;192(8):F21-5. J Exp Med. 2000. PMID: 11034612 Free PMC article. Review. No abstract available.
-
CrmA expression in T lymphocytes of transgenic mice inhibits CD95 (Fas/APO-1)-transduced apoptosis, but does not cause lymphadenopathy or autoimmune disease.EMBO J. 1996 Oct 1;15(19):5167-76. EMBO J. 1996. PMID: 8895561 Free PMC article.
-
CD40 activation induces apoptosis in cultured human hepatocytes via induction of cell surface fas ligand expression and amplifies fas-mediated hepatocyte death during allograft rejection.J Exp Med. 1999 Jan 18;189(2):441-6. doi: 10.1084/jem.189.2.441. J Exp Med. 1999. PMID: 9892626 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous