Chapter Eight - Hyperosmotic Activation of the CD95 System
Section snippets
INTRODUCTION
Apoptosis is characterized by cell shrinkage, nuclear condensation, DNA fragmentation, and apoptotic body formation. These features separate apoptosis from other forms of cell death, such as necrosis (Kerr et al., 1974). It is well known that shrunken hepatocytes are more susceptible to stress‐induced cell death, which may explain the clinical observation that transplantation of livers from hypernatremic donors shows high rates of primary graft dysfunction. Apoptotic volume decrease (AVD) is an
HYPEROSMOTIC ACTIVATION OF THE CD95 SYSTEM IN HEPATOCYTES
Whereas CD95 in normosmotically exposed rat hepatocytes is localized inside the cells and exhibits no detectable membrane localization, this death receptor is rapidly targeted to the plasma membrane in response to proapoptotic stimuli, such as hyperosmotic exposure, CD95L, or bile acids (Eberle et al., 2005, Eberle et al., 2007, Reinehr and Häussinger, 2004, Reinehr et al., 2002, Reinehr et al., 2003a, Reinehr et al., 2003b, Reinehr et al., 2004a, Reinehr et al., 2004b, Reinehr et al., 2004c).
CONCLUDING REMARKS
Hyperosmotic hepatocyte shrinkage sensitizes the cells toward CD95 ligand‐induced apoptosis by activating the CD95 system. Figure 8.3 summarizes our current view on the signaling events involved in hyperosmotic activation of the CD95 system in hepatocytes. The hyperosmotically induced cascade of signaling events starts with endosomal acidification triggering an ASM‐derived increase in the intracellular ceramide concentration, which leads via PKCζ and p47phox to NADPH oxidase activation and
ACKNOWLEDGMENTS
Our studies were supported by Deutsche Forschungsgemeinschaft (DFG) through Sonderforschungsbereich 575 “Experimentelle Hepatologie” (Düsseldorf). Excellent work by Stephan Becker, Andrea Eberle, Boris Görg, Elisabeth Winands, and Claudia Rupprecht is gratefully acknowledged.
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Reactive oxygen species activated NLRP3 inflammasomes initiate inflammation in hyperosmolarity stressed human corneal epithelial cells and environment-induced dry eye patients
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Cell Volume Control
2013, Seldin and Geibisch's The KidneyCell Volume Control
2012, Seldin and Giebisch's The Kidney: Physiology and PathophysiologyCD95 death receptor and epidermal growth factor receptor (EGFR) in liver cell apoptosis and regeneration
2012, Archives of Biochemistry and BiophysicsCitation Excerpt :Then, the role of EGFR in activating CD95 death receptor in hepatocytes is described. In hepatocytes, the complex and c-Jun-N-terminal-kinase (JNK)-dependent interplay between EGFR and CD95 leading to EGFR-mediated CD95 tyrosine phosphorylation and subsequent apoptosis has been studied in detail (for review see [3,4,6]). In contrast to hepatocytes, in hepatic stellate cells (HSC) pro-apoptotic stimuli like CD95 ligand (CD95L) or hydrophobic bile acids fail to induce a sustained JNK-activation and apoptotic HSC death [2,7].