Journal article
Switch from type II to I Fas/CD95 death signaling on in vitro culturing of primary hepatocytes
D Walter, K Schmich, S Vogel, R Pick, T Kaufmann, FC Hochmuth, A Haber, K Neubert, S McNelly, F von Weizsäcker, I Merfort, U Maurer, A Strasser, C Borner
Hepatology | WILEY | Published : 2008
DOI: 10.1002/hep.22541
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..
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Awarded by National Cancer Institute
Funding Acknowledgements
This work was supported by the Hepatosys program of the Bundesministerium fur Bildung and forschung (to C.B., D.W., R.P., K.S., I.M., and F.vW) and the Spemann Graduate School of Biology and Medicine of the Deutsche forschungsgemeinschaft (GSC-4) (to C.B and S.V.). A.S. and T.K. were supported by grants (program 257502) and fellowships from the Australian National Health and Medical Research Council (Canberra), the National Cancer Institute (U.S. National institute of Health; CA80188, CA 43540), the Leukemia and Lymphoma Society of America (SCOR grant 7015), the Juvenile Diabetes Research Foundation/NHMRC, the Swiss National Science Foundation, the Roche Research Foundation, and the Novartis Foundations (to T.K)