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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...

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Autores principales: Nakamichi, Ikuo, Toivola, Diana M., Strnad, Pavel, Michie, Sara A., Oshima, Robert G., Baribault, Hélène, Omary, M. Bishr
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
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.
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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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