Switch from Type II to I Fas/CD95 Death Signaling on In Vitro Culturing of Primary Hepatocytes
- Author(s)
- Walter, D; Schmich, K; Vogel, S; Pick, R; Kaufmann, T; Hochmuth, FC; Haber, A; Neubert, K; McNelly, S; von Weizsaecker, F; Merfort, I; Maurer, U; Strasser, A; Borner, C;
- Details
- Publication Year 2008-12,Volume 48,Issue #6,Page 1942-1953
- Journal Title
- HEPATOLOGY
- Publication Type
- Journal Article
- Abstract
- 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 (TNF alpha/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. (HEPATOLOGY 2008;48:1942-1953.)
- Publisher
- JOHN WILEY & SONS INC
- Keywords
- CELL-DEATH; MITOCHONDRIAL RELEASE; LIVER-INJURY; APOPTOSIS; FAS; PROTEIN; BCL-2; RECEPTOR; INHIBITION; ACTIVATION
- Publisher's Version
- https://doi.org/10.1002/hep.22541
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2008-12-01 12:00:00