Increased P-type ATPase activity in Leishmania tropica resistant to methotrexate.
In the present report, we show evidence that the membrane from the protozoan parasite Leishmania tropica (LRC-L39), in vitro resistant to 1 mM of methotrexate (MTX), has a significative increased ATPase activity with respect to wild-type line. This ATPase activity is vanadate sensitive, a characteristic of the P-type ATPases included in the ATP-binding casette (ABC) superfamily of transporters, such as P-glycoprotein involved in the multidrug resistance in mammalian cells. Also, this ATPase activity is not modified by MTX, ammonium molybdate and other detergents such as Triton X-100, Brij 58 and lysophosphatidylcholine. However, unlike the P-glycoprotein, we have observed that the ATPase activity is not stimulated by the drugs verapamil and puromycin. This significative ATPase activity could be related to the overexpressed putative P-glycoprotein, with unknown function in these MTX-resistant parasites.
Sanchez
A
A
Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
Castanys
S
S
Gamarro
F
F
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D002462:Cell Membrane / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology*; D007700:Kinetics; D007895:Leishmania tropica / Q000187:drug effects* / Q000201:enzymology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008727:Methotrexate / Q000633:toxicity*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D000251:Adenosine Triphosphatases; D008727:Methotrexate