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Keratin 8 overexpression promotes mouse Mallory body formation
Keratins 8 and 18 (K8/18) are major constituents of Mallory bodies (MBs), which are hepatocyte cytoplasmic inclusions seen in several liver diseases. K18-null but not K8-null or heterozygous mice form MBs, which indicates that K8 is important for MB formation. Early stages in MB genesis include K8/1...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171301/ https://www.ncbi.nlm.nih.gov/pubmed/16365160 http://dx.doi.org/10.1083/jcb.200507093 |
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author | Nakamichi, Ikuo Toivola, Diana M. Strnad, Pavel Michie, Sara A. Oshima, Robert G. Baribault, Hélène Omary, M. Bishr |
author_facet | Nakamichi, Ikuo Toivola, Diana M. Strnad, Pavel Michie, Sara A. Oshima, Robert G. Baribault, Hélène Omary, M. Bishr |
author_sort | Nakamichi, Ikuo |
collection | PubMed |
description | Keratins 8 and 18 (K8/18) are major constituents of Mallory bodies (MBs), which are hepatocyte cytoplasmic inclusions seen in several liver diseases. K18-null but not K8-null or heterozygous mice form MBs, which indicates that K8 is important for MB formation. Early stages in MB genesis include K8/18 hyperphosphorylation and overexpression. We used transgenic mice that overexpress K8, K18, or K8/18 to test the importance of K8 and/or K18 in MB formation. MBs were induced by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Livers of young K8 or K8/K18 overexpressors had no histological abnormalities despite increased keratin protein and phosphorylation. In aging mice, only K8-overexpressing livers spontaneously developed small “pre-MB” aggregates. Only K8-overexpressing young mice are highly susceptible to MB formation after short-term DDC feeding. Thus, the K8 to K18 ratio, rather than K8/18 overexpression by itself, plays an essential role in MB formation. K8 overexpression is sufficient to form pre-MB and primes animals to accumulate MBs upon DDC challenge, which may help explain MB formation in human liver diseases. |
format | Text |
id | pubmed-2171301 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21713012008-03-05 Keratin 8 overexpression promotes mouse Mallory body formation Nakamichi, Ikuo Toivola, Diana M. Strnad, Pavel Michie, Sara A. Oshima, Robert G. Baribault, Hélène Omary, M. Bishr J Cell Biol Research Articles Keratins 8 and 18 (K8/18) are major constituents of Mallory bodies (MBs), which are hepatocyte cytoplasmic inclusions seen in several liver diseases. K18-null but not K8-null or heterozygous mice form MBs, which indicates that K8 is important for MB formation. Early stages in MB genesis include K8/18 hyperphosphorylation and overexpression. We used transgenic mice that overexpress K8, K18, or K8/18 to test the importance of K8 and/or K18 in MB formation. MBs were induced by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Livers of young K8 or K8/K18 overexpressors had no histological abnormalities despite increased keratin protein and phosphorylation. In aging mice, only K8-overexpressing livers spontaneously developed small “pre-MB” aggregates. Only K8-overexpressing young mice are highly susceptible to MB formation after short-term DDC feeding. Thus, the K8 to K18 ratio, rather than K8/18 overexpression by itself, plays an essential role in MB formation. K8 overexpression is sufficient to form pre-MB and primes animals to accumulate MBs upon DDC challenge, which may help explain MB formation in human liver diseases. The Rockefeller University Press 2005-12-19 /pmc/articles/PMC2171301/ /pubmed/16365160 http://dx.doi.org/10.1083/jcb.200507093 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Nakamichi, Ikuo Toivola, Diana M. Strnad, Pavel Michie, Sara A. Oshima, Robert G. Baribault, Hélène Omary, M. Bishr Keratin 8 overexpression promotes mouse Mallory body formation |
title | Keratin 8 overexpression promotes mouse Mallory body formation |
title_full | Keratin 8 overexpression promotes mouse Mallory body formation |
title_fullStr | Keratin 8 overexpression promotes mouse Mallory body formation |
title_full_unstemmed | Keratin 8 overexpression promotes mouse Mallory body formation |
title_short | Keratin 8 overexpression promotes mouse Mallory body formation |
title_sort | keratin 8 overexpression promotes mouse mallory body formation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171301/ https://www.ncbi.nlm.nih.gov/pubmed/16365160 http://dx.doi.org/10.1083/jcb.200507093 |
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