Aureobasidin A, an antifungal cyclic depsipeptide antibiotic, is a substrate for both human MDR1 and MDR2/P-glycoproteins
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- 作者：Kino ; Kouichi ; Taguchi ; Yoshitomo ; Yamada ; Kouji ; Komano ; Tohru ; Ueda ; Kazumitsu
- 关键词：ABC transporter ; P-glycoprotein ; MDR1 ; MDR2 ; Aureobasidin A ; Drug resistance ; Saccharomyces cerevisiae
- 刊名：FEBS Letters
- 出版年：1996
- 出版时间：December 9, 1996
- 年：1996
- 卷：399
- 期：1-2
- 页码：29-32
- 全文大小：467 K
文摘
The human MDR1 gene encodes the multidrug transporter P-glycoprotein (Pgp). Although the MDR2/Pgp shares about 80 % identity at the amino acid level with the MDR1/Pgp, the MDR2/Pgp cannot act as a multidrug transporter. We examined the drug sensitivity of Saccharomyces cerevisiae expressing either the human MDR1/Pgp or MDR2/Pgp. The human MDR1/Pgp conferred about 4-fold resistance to aureobasidin A, a cyclic depsipeptide antifungal antibiotic, on the drug-sensitive yeast strains. Interestingly the human MDR2/Pgp also conferred about 2.5-fold resistance to aureobasidin A. The resistance to aureobasidin A conferred by the MDR2/Pgp as well as by the MDR1/Pgp was overcome by vinblastine, verapamil, and cyclosporin A, depending on their concentrations, but not by colchicine. Aureobasidin A probably interacts directly with Pgps, because it overcame multidrug resistance of human cells and inhibited azidopine photoaffinity labeling of MDR1/Pgp in human cell membranes. These results suggest the possibility that the human MDR1 and MDR2/Pgps have conserved domain(s) for drug recognition.