Switch from Type II to I Fas/CD95 Death Signaling on in Vitro Culturing of Primary Hepatocytes

Overview

Journal Hepatology

Specialty Gastroenterology

Date 2008 Nov 13

PMID 19003879

Citations 25

Authors

Dorothee Walter

Kathrin Schmich

Sandra Vogel

Robert Pick

Thomas Kaufmann

Florian Christoph Hochmuth

Angelika Haber

Karin Neubert

Sabine McNelly

Fritz von Weizsacker

Irmgard Merfort

Ulrich Maurer

Andreas Strasser

Christoph Borner

Affiliations

Soon will be listed here.

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.

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References

Hueber A, Bernard A, Herincs Z, Couzinet A, He H . An essential role for membrane rafts in the initiation of Fas/CD95-triggered cell death in mouse thymocytes. EMBO Rep. 2002; 3(2):190-6. PMC: 1083963. DOI: 10.1093/embo-reports/kvf022. View

Smyth L, Brady H . cMet and Fas receptor interaction inhibits death-inducing signaling complex formation in endothelial cells. Hypertension. 2005; 46(1):100-6. DOI: 10.1161/01.HYP.0000167991.82153.16. View

Holler N, Tardivel A, Kovacsovics-Bankowski M, Hertig S, Gaide O, Martinon F . Two adjacent trimeric Fas ligands are required for Fas signaling and formation of a death-inducing signaling complex. Mol Cell Biol. 2003; 23(4):1428-40. PMC: 141146. DOI: 10.1128/MCB.23.4.1428-1440.2003. View

Kaufmann T, Tai L, Ekert P, Huang D, Norris F, Lindemann R . The BH3-only protein bid is dispensable for DNA damage- and replicative stress-induced apoptosis or cell-cycle arrest. Cell. 2007; 129(2):423-33. DOI: 10.1016/j.cell.2007.03.017. View

Klingmuller U, Bauer A, Bohl S, Nickel P, Breitkopf K, Dooley S . Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways. Syst Biol (Stevenage). 2006; 153(6):433-47. DOI: 10.1049/ip-syb:20050067. View

Yin X, Wang K, Gross A, Zhao Y, Zinkel S, Klocke B . Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature. 1999; 400(6747):886-91. DOI: 10.1038/23730. View

Galle P, Krammer P . CD95-induced apoptosis in human liver disease. Semin Liver Dis. 1998; 18(2):141-51. DOI: 10.1055/s-2007-1007150. View

Du C, Fang M, Li Y, Li L, Wang X . Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell. 2000; 102(1):33-42. DOI: 10.1016/s0092-8674(00)00008-8. View

Peter M, Budd R, Desbarats J, Hedrick S, Hueber A, Newell M . The CD95 receptor: apoptosis revisited. Cell. 2007; 129(3):447-50. DOI: 10.1016/j.cell.2007.04.031. View

10.

Wang X, DeFrances M, Dai Y, Pediaditakis P, Johnson C, Bell A . A mechanism of cell survival: sequestration of Fas by the HGF receptor Met. Mol Cell. 2002; 9(2):411-21. DOI: 10.1016/s1097-2765(02)00439-2. View

11.

Youle R, Strasser A . The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2007; 9(1):47-59. DOI: 10.1038/nrm2308. View

12.

OReilly L, Divisekera U, Newton K, Scalzo K, Kataoka T, Puthalakath H . Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes. Cell Death Differ. 2004; 11(7):724-36. DOI: 10.1038/sj.cdd.4401408. View

13.

Green D, Kroemer G . The pathophysiology of mitochondrial cell death. Science. 2004; 305(5684):626-9. DOI: 10.1126/science.1099320. View

14.

Chang L, Kamata H, Solinas G, Luo J, Maeda S, Venuprasad K . The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover. Cell. 2006; 124(3):601-13. DOI: 10.1016/j.cell.2006.01.021. View

15.

Hewitt N, Lechon M, Houston J, Hallifax D, Brown H, Maurel P . Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev. 2007; 39(1):159-234. DOI: 10.1080/03602530601093489. View

16.

Li S, Zhao Y, He X, Kim T, Kuharsky D, Rabinowich H . Relief of extrinsic pathway inhibition by the Bid-dependent mitochondrial release of Smac in Fas-mediated hepatocyte apoptosis. J Biol Chem. 2002; 277(30):26912-20. DOI: 10.1074/jbc.M200726200. View

17.

Block G, Locker J, BOWEN W, Petersen B, Katyal S, Strom S . Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium. J Cell Biol. 1996; 132(6):1133-49. PMC: 2120765. DOI: 10.1083/jcb.132.6.1133. View

18.

Zhao Y, DiFrancesca D, Wang X, Zarnegar R, Michalopoulos G, Yin X . Promotion of Fas-mediated apoptosis in Type II cells by high doses of hepatocyte growth factor bypasses the mitochondrial requirement. J Cell Physiol. 2007; 213(2):556-63. PMC: 2636794. DOI: 10.1002/jcp.21136. View

19.

Takahashi R, Deveraux Q, Tamm I, Welsh K, Salvesen G, Reed J . A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem. 1998; 273(14):7787-90. DOI: 10.1074/jbc.273.14.7787. View

20.

Peter M, Krammer P . The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ. 2003; 10(1):26-35. DOI: 10.1038/sj.cdd.4401186. View