Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip
Summary 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 prote...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2013-05-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/2/7/695 |
| _version_ | 1819075599224799232 |
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| author | Jongeun Lee Kwi-Hoon Jang Hakhyun Kim Younglan Lim Sujin Kim Han-Na Yoon In Kwon Chung Jürgen Roth Nam-On Ku |
| author_facet | Jongeun Lee Kwi-Hoon Jang Hakhyun Kim Younglan Lim Sujin Kim Han-Na Yoon In Kwon Chung Jürgen Roth Nam-On Ku |
| author_sort | Jongeun Lee |
| collection | DOAJ |
| description | Summary
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. |
| first_indexed | 2024-12-21T18:27:58Z |
| format | Article |
| id | doaj.art-054a2e4b673b401088cc006c5d30c4a0 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-21T18:27:58Z |
| publishDate | 2013-05-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-054a2e4b673b401088cc006c5d30c4a02022-12-21T18:54:22ZengThe Company of BiologistsBiology Open2046-63902013-05-012769570210.1242/bio.2013460620134606Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-FlipJongeun LeeKwi-Hoon JangHakhyun KimYounglan LimSujin KimHan-Na YoonIn Kwon ChungJürgen RothNam-On KuSummary 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.http://bio.biologists.org/content/2/7/695KeratinIntermediate filamentsLiverc-FlipApoptosisNF-κBSAPK |
| spellingShingle | Jongeun Lee Kwi-Hoon Jang Hakhyun Kim Younglan Lim Sujin Kim Han-Na Yoon In Kwon Chung Jürgen Roth Nam-On Ku Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip Biology Open Keratin Intermediate filaments Liver c-Flip Apoptosis NF-κB SAPK |
| title | Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip |
| title_full | Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip |
| title_fullStr | Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip |
| title_full_unstemmed | Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip |
| title_short | Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip |
| title_sort | predisposition to apoptosis in keratin 8 null liver is related to inactivation of nf κb and sapks but not decreased c flip |
| topic | Keratin Intermediate filaments Liver c-Flip Apoptosis NF-κB SAPK |
| url | http://bio.biologists.org/content/2/7/695 |
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