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Lee J, Jang KH, Kim H, et al. Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip. Biol Open. 2013;2(7):695-702doi: 10.1242/bio.20134606.
Lee, J., Jang, K. H., Kim, H., Lim, Y., Kim, S., Yoon, H. N., Chung, I. K., Roth, J., & Ku, N. O. (2013). Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip. Biology open, 2(7), 695-702. https://doi.org/10.1242/bio.20134606
Lee, Jongeun, et al. "Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip." Biology open vol. 2,7 (2013): 695-702. doi: https://doi.org/10.1242/bio.20134606
Lee J, Jang KH, Kim H, Lim Y, Kim S, Yoon HN, Chung IK, Roth J, Ku NO. Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip. Biol Open. 2013 May 29;2(7):695-702. doi: 10.1242/bio.20134606. Print 2013 Jul 15. PMID: 23862017; PMCID: PMC3711037.
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Biol Open. 2013 May 29;2(7):695-702. doi: 10.1242/bio.20134606. Print 2013 Jul 15.

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

Biology open

Jongeun Lee, Kwi-Hoon Jang, Hakhyun Kim, Younglan Lim, Sujin Kim, Han-Na Yoon, In Kwon Chung, Jürgen Roth, Nam-On Ku

Affiliations

  1. Department of Integrated OMICS for Biomedical Science, WCU Program of Graduate School, Yonsei University , Seoul 120-749 , Korea.

PMID: 23862017 PMCID: PMC3711037 DOI: 10.1242/bio.20134606

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 K8-null 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 apoptosis- or cell survival-related proteins demonstrated that inhibition of phosphorylation of NF-κB 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-κB is rapidly depleted through Fas-mediated apoptosis. Notably, we found that NF-κB 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.

Keywords: Apoptosis; Intermediate filaments; Keratin; Liver; NF-κB; SAPK; c-Flip

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