Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-kB and SAPKs but not decreased c-Flip

Abstract

Keratin 8 and 18 (K8/K18) are major intermediate filament proteins of liver hepatocytes. They provide mechanical and nonmechanical stability, thereby protecting cells from stress. Hence, K8-null mice are highly sensitive to Fas-mediated liver cell apoptosis. However, the role of c-Flip protein in K8null related susceptibility to liver injury is controversial. Here we analyzed c-Flip protein expression in various K8 or K18 null/mutant transgenic livers and show that they are similar in all analyzed transgenic livers and that previously reported c-Flip protein changes are due to antibody cross-reaction with mouse K18. Furthermore, analysis of various apoptosisor cell survival-related proteins demonstrated that inhibition of phosphorylation of NF-kB and various stress activated protein kinases (SAPKs), such as p38 MAPK, p44/42 MAPK and JNK1/2, is related to the higher sensitivity of K8-null hepatocytes whose nuclear NF-kB is rapidly depleted through Fas-mediated apoptosis. Notably, we found that NFkB and the studied protein kinases are associated with the K8/ K18 complex and are released upon phosphorylation. Therefore, interaction of keratins with cell survival-related protein kinases and transcription factors is another important factor for hepatocyte survival.

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Cite this paper

@inproceedings{Lee2013PredispositionTA, title={Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-kB and SAPKs but not decreased c-Flip}, author={Jongeun Lee and Kwi-Hoon Jang and Hakhyun Kim and Younglan Lim and Sujin Kim and Han-Na Yoon and In Kwon Chung and J{\"{u}rgen Roth}, year={2013} }