scholarly journals Keratin 8 overexpression promotes mouse Mallory body formation

2005 ◽  
Vol 171 (6) ◽  
pp. 931-937 ◽  
Author(s):  
Ikuo Nakamichi ◽  
Diana M. Toivola ◽  
Pavel Strnad ◽  
Sara A. Michie ◽  
Robert G. Oshima ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Liver Diseases ◽  
Human Liver ◽  
Essential Role ◽  
Short Term ◽  
Cytoplasmic Inclusions ◽  
Body Formation ◽  
Early Stages ◽  
Mallory Bodies ◽  
Keratin 8

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.

scholarly journals Short-term dexamethasone treatment inhibits vein graft thickening in hypercholesterolemic ApoE3Leiden transgenic mice

2006 ◽  
Vol 43 (4) ◽  
pp. 809-815 ◽  
Author(s):  
Abbey Schepers ◽  
Nuno M.M. Pires ◽  
Daniel Eefting ◽  
Margreet R. de Vries ◽  
J. Hajo van Bockel ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Vein Graft ◽  
Dexamethasone Treatment ◽  
Short Term

scholarly journals Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) in Eμ-pim-1 transgenic mice

1996 ◽  
Vol 17 (10) ◽  
pp. 2221-2227 ◽  
Author(s):  
Ilona Kryspin Sørensen ◽  
Alicja Mortensen ◽  
Eva Kristiansen ◽  
Coen van Kreijl ◽  
Richard H. Adamson ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Short Term

Detection of a Microsomal Antigen and Its Antibody in Human Liver Diseases

1979 ◽  
Vol 59 (4) ◽  
pp. 459-464 ◽  
Author(s):  
E. Penner ◽  
S.O. Emejuaiwe ◽  
F. Milgrom
Keyword(s):  
Liver Diseases ◽  
Human Liver ◽  
Microsomal Antigen

scholarly journals Biology of the immunomodulatory molecule HLA-G in human liver diseases

2015 ◽  
Vol 62 (6) ◽  
pp. 1430-1437 ◽  
Author(s):  
Laurence Amiot ◽  
Nicolas Vu ◽  
Michel Samson
Keyword(s):  
Liver Diseases ◽  
Human Liver

Redefining the Issues: NGO Influence on International Forest Negotiations

2004 ◽  
Vol 4 (2) ◽  
pp. 51-74 ◽  
Author(s):  
David Humphreys
Keyword(s):  
Nongovernmental Organizations ◽  
United Nations ◽  
International Politics ◽  
Forest Policy ◽  
Time Frame ◽  
Short Term ◽  
Early Stages ◽  
The United Nations ◽  
International Forest Policy ◽  
Environmental Challenge

How successful have nongovernmental organizations (NGOs) been in influencing international forest policy? Specifically, how effective have they been at altering the texts of international forest policy declarations and agreements? This paper studies NGO efforts to influence international forest policy from the mid-1980s, when deforestation first emerged as an international environmental challenge, to 2001 when the United Nations Forum on Forests was created. This paper demonstrates that, in the short term, NGOs are more effective when they: 1. involve themselves in the early stages of negotiations, 2. suggest substantive and procedural ideas that are already well-known in fora outside forest politics, and 3. align their suggestions with the prevailing neoliberal discourse of international politics. The paper suggests that such conditions can be rather limited and thus speculates about NGO efforts within a longer time frame.

scholarly journals Formation of Mallory Body-like Inclusions and Cell Death Induced by Deregulated Expression of Keratin 18

2002 ◽  
Vol 13 (10) ◽  
pp. 3441-3451 ◽  
Author(s):  
Ikuo Nakamichi ◽  
Shigetsugu Hatakeyama ◽  
Keiichi I. Nakayama
Keyword(s):  
Cell Death ◽  
Important Determinant ◽  
Cellular Model ◽  
Microtubule Network ◽  
Cytoplasmic Inclusions ◽  
Mallory Bodies ◽  
Keratin 18 ◽  
Intracellular Aggregates

Mallory bodies (MBs) are cytoplasmic inclusions that contain keratin 8 (K8) and K18 and are present in hepatocytes of individuals with alcoholic liver disease, nonalcoholic steatohepatitis, or benign or malignant hepatocellular neoplasia. Mice fed long term with griseofulvin are an animal model of MB formation. However, the lack of a cellular model has impeded understanding of the molecular mechanism of this process. Culture of HepG2 cells with griseofulvin has now been shown to induce both the formation of intracellular aggregates containing K18 as well as an increase in the abundance of K18 mRNA. Overexpression of K18 in HepG2, HeLa, or COS-7 cells also induced the formation of intracellular aggregates that stained with antibodies to ubiquitin and with rhodamine B (characteristics of MBs formed in vivo), eventually leading to cell death. The MB-like aggregates were deposited around centrosomes and disrupted the microtubular array. Coexpression of K8 with K18 restored the normal fibrous pattern of keratin distribution and reduced the toxicity of K18. In contrast, an NH2-terminal deletion mutant of K8 promoted the formation of intracellular aggregates even in the absence of K18 overexpression. Deregulated expression of K18, or an imbalance between K8 and K18, may thus be an important determinant of MB formation, which compromises the function of centrosomes and the microtubule network and leads to cell death.

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