Aureobasidin A, an antifungal cyclic depsipeptide antibiotic, is a substrate for both human MDR1 and MDR2/P‐glycoproteins

FEBS Letters

Taguchi, Yoshitomo¹  Yamada, Kouji¹  Komano, Tohru¹  Kino, Kouichi¹  Ueda, Kazumitsu¹ 

[1] Laboratory of Biochemistry, Department of Agricultural Chemistry, Kyoto University, Kyoto 606-01, Japan

关键词: ABC transporter;    P-glycoprotein;    MDR1;    MDR2;    Aureobasidin A;    Drug resistance;    Saccharomyces cerevisiae;    MDR;    multidrug resistance;    Pgp;    P-glycoprotein;    PCR;    polymerase chain reactions;    aa;    amino acid(s);   

DOI  :  10.1016/S0014-5793(96)01265-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 MDRI/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 MDRI/Pgp in human cell membranes. These results suggest the possibility that the human MDR1 and MDR2/Pgps have conserved domain(s) for drug recognition.

【 授权许可】

Unknown