Putative P-glycoprotein expression in arsenite-resistant Leishmania donovani down-regulated by verapamil.
Western immunoblots of whole cell lysate and crude membrane extract of an in vitro selected sodium m-arsenite-resistant L. donovani strain revealed a 230-kDa protein identified by an anti-P-glycoprotein (Pgp) antibody. Immunofluorescence microscopy, using the same antibody, detected putative Pgp on resistant parasites. Overexpression of the putative Pgp was down-regulated by verapamil. These results provided, possibly, the first evidence that (i) overexpression of Pgp-like protein occurs in arsenite-resistant Leishmania that are cross-resistant to structurally and functionally unrelated drugs and (ii) verapamil regulates drug sensitivity possibly by down-regulating Pgp expression in the arsenite-resistant Leishmania.
Kaur
J
J
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Punjab, 160 062, India.
Dey
C S
CS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D015151:Immunoblotting; D007893:Leishmania donovani / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018053:Arsenites; D014700:Verapamil; C015001:arsenite