| Effect of glucocorticoids on alkaline phosphatase, alanine aminotransferase, and gamma-glutamyltransferase in cultured dog hepatocytes. | |
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MedLine Citation:
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PMID: 1979772 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucocorticoid(GC)-induced hepatopathy in the dog is characterized by abnormal liver morphology and increases in serum alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), and the liver alkaline phosphatase isoenzyme (LALP) and by the appearance of an unusual isoenzyme of alkaline phosphatase known as the corticosteroid-induced alkaline phosphatase isoenzyme (CALP). It has not been shown whether the increases in serum ALT, GGT, and LALP are as a result of an increase in production of these enzymes or as a result of the GC-induced hepatocellular swelling and possible membrane alterations. Also, it has been assumed that the mechanism of production of CALP is via GC-induced gene derepression and de novo protein synthesis; however, this hypothesis has not been directly tested. Using isolated dog hepatocytes maintained in a confluent monolayer culture in the presence and absence of GC or cyclic AMP, no statistical increase in serum ALT, GGT, or LALP was observed. A combination of GC and cyclic AMP also caused no statistical increase in ALT and GGT; however, we demonstrate that these conditions clearly stimulated the de novo synthesis of LALP. These conditions do not induce the synthesis of CALP as determined by a sensitive immunoassay. The data obtained using this in vitro model suggest that the primary mechanism(s) of the in vivo increase of serum ALT and GGT in GC treated dogs may be other than that of de novo protein synthesis. Likewise, in vitro production of CALP may be a mechanism more complex than the conditions tested in this study. |
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Authors:
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S P Hadley; W E Hoffmann; M S Kuhlenschmidt; R K Sanecki; J L Dorner |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Enzyme Volume: 43 ISSN: 0013-9432 ISO Abbreviation: Enzyme Publication Date: 1990 |
Date Detail:
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Created Date: 1991-02-01 Completed Date: 1991-02-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1262265 Medline TA: Enzyme Country: SWITZERLAND |
Other Details:
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Languages: eng Pagination: 89-98 Citation Subset: IM |
Affiliation:
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Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alanine Transaminase
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drug effects* Alkaline Phosphatase / drug effects* Animals Cells, Cultured Cyclic AMP / pharmacology Cycloheximide / pharmacology DNA / analysis Dactinomycin / pharmacology Dogs Glucocorticoids / pharmacology* Immunoassay Isoenzymes / drug effects Liver / cytology, drug effects, enzymology* gamma-Glutamyltransferase / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Glucocorticoids; 0/Isoenzymes; 50-76-0/Dactinomycin; 60-92-4/Cyclic AMP; 66-81-9/Cycloheximide; 9007-49-2/DNA; EC 2.3.2.2/gamma-Glutamyltransferase; EC 2.6.1.2/Alanine Transaminase; EC 3.1.3.1/Alkaline Phosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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