Document Detail


Connexin 32 dominant-negative mutant transgenic rats are resistant to hepatic damage by chemicals.
MedLine Citation:
PMID:  15239104     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Connexins are subunits of gap junction channels, which allow direct transfer of ions, secondary messenger molecules, and other metabolites between contacting cells. Gap junctions are believed to be involved in tissue homeostasis, embryonic development, and control of cell proliferation. Several studies have shown that cell damage signals are transmitted through gap junctions when cells are irradiated or when cells bearing the herpes simplex virus-thymidine kinase (HSV-TK) gene are treated with ganciclovir. We established 2 lines of transgenic rats with a dominant-negative mutant of connexin 32 gene under control of the albumin promoter. In the livers of transgenic rats, membrane localization of normal endogenous connexin 32 protein is disturbed, and gap junction capacity measured by scrape dye-transfer assay in vivo is markedly decreased when compared with wild-type rats. The present investigation concerned susceptibility to the liver-toxic substances D-galactosamine and carbon tetrachloride. These toxicants induced massive liver cell death and elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the wild-type rats; however, much fewer liver cells were damaged and serum enzyme elevation was much lower in the transgenic rats. In conclusion, gap junctional intercellular communication (GJIC) plays an important role in toxic effects of chemicals; damage or death signals may pass through gap junctions in the rat liver in vivo.
Authors:
Makoto Asamoto; Naomi Hokaiwado; Toshiya Murasaki; Tomoyuki Shirai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  40     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-07     Completed Date:  2004-07-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  205-10     Citation Subset:  IM    
Affiliation:
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
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MeSH Terms
Descriptor/Qualifier:
Alanine Transaminase / blood
Animals
Animals, Genetically Modified
Aspartate Aminotransferases / blood
Carbon Tetrachloride Poisoning*
Connexins / genetics*,  metabolism
Drug Resistance / genetics
Female
Galactosamine / chemistry,  poisoning*
Gap Junctions / physiology
Gene Dosage
Gene Expression
Genes, Dominant*
Liver / drug effects*,  metabolism,  pathology
Male
Mutation / physiology*
Necrosis
Rats
Stereoisomerism
Chemical
Reg. No./Substance:
0/Connexins; 0/connexin 32; 7535-00-4/Galactosamine; EC 2.6.1.1/Aspartate Aminotransferases; EC 2.6.1.2/Alanine Transaminase

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