Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Hepatology ; 48(6): 1942-53, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19003879

ABSTRACT

UNLABELLED: Fas/CD95-induced apoptosis of hepatocytes in vivo proceeds through the so-called type II pathway, requiring the proapoptotic BH3-only Bcl-2 family member Bid for mitochondrial death signaling. Consequently, Bid-deficient mice are protected from anti-Fas antibody injection induced fatal hepatitis. We report the unexpected finding that freshly isolated mouse hepatocytes, cultured on collagen or Matrigel, become independent of Bid for Fas-induced apoptosis, thereby switching death signaling from type II to type I. In such in vitro cultures, Fas ligand (FasL) activates caspase-3 without Bid cleavage, Bax/Bak activation or cytochrome c release, and neither Bid ablation nor Bcl-2 overexpression is protective. The type II to type I switch depends on extracellular matrix adhesion, as primary hepatocytes in suspension die in a Bid-dependent manner. Moreover, the switch is specific for FasL-induced apoptosis as collagen-plated Bid-deficient hepatocytes are protected from tumor necrosis factor alpha/actinomycin D (TNFalpha/ActD)-induced apoptosis. CONCLUSION: Our data suggest a selective crosstalk between extracellular matrix and Fas-mediated signaling that favors mitochondria-independent type I apoptosis induction.


Subject(s)
Apoptosis/physiology , Hepatocytes/metabolism , Signal Transduction/physiology , fas Receptor/metabolism , Animals , BH3 Interacting Domain Death Agonist Protein/metabolism , Caspase 3/metabolism , Cell Adhesion/physiology , Cells, Cultured , Extracellular Matrix/metabolism , Fas Ligand Protein/metabolism , Hepatocytes/cytology , Mice , Mice, Knockout , Mitochondria, Liver/metabolism , Models, Animal , Tumor Necrosis Factor-alpha/metabolism , bcl-2 Homologous Antagonist-Killer Protein/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...