| First Author | Lee J | Year | 2013 |
| Journal | Biol Open | Volume | 2 |
| Issue | 7 | Pages | 695-702 |
| PubMed ID | 23862017 | Mgi Jnum | J:199436 |
| Mgi Id | MGI:5502788 | Doi | 10.1242/bio.20134606 |
| Citation | Lee J, et al. (2013) Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-kappaB and SAPKs but not decreased c-Flip. Biol Open 2(7):695-702 |
| abstractText | 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-kappaB 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-kappaB is rapidly depleted through Fas-mediated apoptosis. Notably, we found that NF-kappaB 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. |
