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KMID : 0614020050200010020
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Journal of Pharmaceutical Sciences (C.N.U.)
2005 Volume.20 No. 1 p.20 ~ p.40
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Methods for Determination of Insulin Signaling in Regulation of Drug Metabolizing Enzyme Expression
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Kim Sang-K,
Oh Soo-J.
Oh Jung-M.
Kim Bong-Hee
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Abstract
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Expression of drug-metabolizing enzymes may be altered in response to development, aging, gender, genetics, nutrition, pregnancy, disease states such as diabetes, long-term alcohol consumption, and inflammation, and by xenobiotics. Although the mechanisms by which xenobiotics regulate drug-metabolizing enzymes have been intensively studied, relatively little is known regarding the cellular mechanisms by which drug-metabolizing enzymes are regulated in response to endogenous factors such as hormones and growth factors. The first major section of this review defines the major insulin-mediated signaling pathways implicated in regulating drug-metabolizing enzyme expression. The second major section of the review presents a summary and evaluation of methods for determination of the role and function of signaling pathways that are involved in the regulation of drug-metabolizing enzyme gene and protein expression, including methods for determination of kinase activity and phosphorylation, the use of kinase inhibitors and dominant-negative protein kinase constructs, and the application of new RNA interference methods.
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KEYWORD
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Drug metabolizing enzyme, insulin signaling, protein kinase, RNA interference, dominant negative construct
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