Kawase Atsushi
Department of Pharmacy, Faculty of Pharmacy, Kinki University.
Yakugaku Zasshi. 2014;134(9):925-9. doi: 10.1248/yakushi.14-00160.
Pathophysiological changes in infection or inflammation are associated with alterations in the production of numerous absorption-, distribution-, metabolism-, and excretion-related proteins. However, little information is available on the effects of inflammation on the expression levels and activities of ATP-binding cassette (ABC) transporters. We examined the effects of acute (on day 7) and chronic (on day 21) inflammation on the expression of ABC transporters in some major tissues in rats. Adjuvant-induced arthritis (AA) in rats was used as an animal model of inflammation. The mRNA levels of mdr1a and mdr1b encoding P-glycoprotein (P-gp) decreased significantly in the liver of AA rats on day 21. Hepatic protein levels of P-gp, Mrp2, and Bcrp decreased significantly in the membrane but not in the homogenate of AA rats after 7 days and after 21 days of treatment with adjuvant. Recently, ezrin/radixin/moesin (ERM) proteins have been found to show linker activity for some transporters and F-actin. We examined the expression levels and functions of ERM proteins in AA because the membrane localization of ABC transporters was decreased without any change in total expression levels. In this review, we summarize our recent work and reports of ERM proteins relevant to ABC transporters.
感染或炎症中的病理生理变化与众多与吸收、分布、代谢和排泄相关的蛋白质的产生改变有关。然而，关于炎症对ATP结合盒（ABC）转运蛋白表达水平和活性的影响，目前所知甚少。我们研究了急性（第7天）和慢性（第21天）炎症对大鼠一些主要组织中ABC转运蛋白表达的影响。大鼠佐剂性关节炎（AA）被用作炎症动物模型。在第21天，编码P-糖蛋白（P-gp）的mdr1a和mdr1b的mRNA水平在AA大鼠肝脏中显著降低。在佐剂处理7天和21天后，AA大鼠肝脏膜中P-gp、Mrp2和Bcrp的蛋白水平显著降低，但匀浆中未降低。最近，埃兹蛋白/根蛋白/膜突蛋白（ERM）已被发现对某些转运蛋白和F-肌动蛋白具有连接活性。由于ABC转运蛋白的膜定位降低而总表达水平没有任何变化，我们研究了AA中ERM蛋白的表达水平和功能。在这篇综述中，我们总结了我们最近关于与ABC转运蛋白相关的ERM蛋白的工作和报告。
