Profiling of hepatic metabolizing enzymes and nuclear receptors in rats with adjuvant arthritis by targeted proteomics

被引：10

作者：

Kawase, Atsushi ^{[1
]}

Tateishi, Shunsuke ^{[1
]}

Kazaoka, Akira ^{[1
]}

机构：

[1] Kindai Univ, Dept Pharm, Fac Pharm, 3-4-1 Kowakae, Higashiosaka, Osaka 5778502, Japan

来源：

BIOPHARMACEUTICS & DRUG DISPOSITION | 2018年 / 39卷 / 06期

关键词：

cytochrome P450; inflammation; metabolism; microsomes; nuclear receptor; BILIRUBIN CLEARANCE; CYTOCHROMES P450; DRUG-METABOLISM; CAR; INFLAMMATION; PROPRANOLOL; LIVER; EXPRESSION; INDUCTION; PROTEIN;

D O I：

10.1002/bdd.2147

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Inflammatory conditions alter the expression and activity of factors influencing pharmacokinetics, such as metabolizing enzymes. The study examined alterations of hepatic protein levels of cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT) and nuclear receptors in rats with adjuvant-induced arthritis (AA rats), an inflammatory animal model, by liquid chromatography-tandem mass spectrometry-based targeted proteomics. The protein levels of CYP1A1, CYP1A2, CYP2A1, CYP2A3, CYP2C6, CYP2C12, CYP2D3, CYP2E1, CYP3A9, UGT1A1 and UGT1A2/3 in liver microsomes of AA rats were significantly lower than those in control rats. The protein levels of constitutive androstane receptor (CAR) and retinoid X receptor (RXR alpha) in the cytoplasm and nucleus were also significantly decreased, to approximately 60% of the control levels. The decreased protein levels of CYP1A2, CYP2C6, CYP2D3, CYP2E1 and UGT1A1 were potentially associated with downregulation of CAR or RXR alpha expression in the nucleus.

引用

页码：308 / 314

页数：7

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