1921
Volume 45, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
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Abstract

Abstract

Multidrug-resistance (MDR) in neoplastic cells is frequently characterized by the overexpression of P-glycoprotein (PGP), a 170 kDa transmembrane glycoprotein that binds multiple cytotoxic drugs as well as calcium channel antagonists. Chloroquine resistance in appears to be analogous to MDR in neoplastic cells, where the induction of resistance with one drug confers resistance to other structurally and functionally unrelated drugs. To test the hypothesis that chloroquine resistance in and antimony resistance in is mediated by a similar mechanism of MDR in mammalian neoplastic cells, a PGP-specific monoclonal antibody (C219) was used to determine the presence of PGP genes in resistant and sensitive and parasites by indirect immunofluorescence assays and Western blotting procedures. These PGP-like components were detected in both drug-sensitive and -resistant and cells. A 40–42 kDa component was observed to be greater in a chloroquine resistant (C line) than in a chloroquine-susceptible P line. Differences observed between Pentostam-resistant and -sensitive promastigote clones and isolates included the increased expression of 96–106 and 23–25 kDa peptides in drug-resistant , and increased amounts of two different peptides in two drug-resistant clones (i.e., 96–106 and 43–45 kDa in WR-746-CL4, and 53 and 23–25 kDa in WR-746-CL6). Interestingly, C219 detected a peptide of the same molecular weight (170 kDa) in amastigotes as in MDR KB carcinoma cells (KB-V1).

Comparative indirect immunofluorescent studies suggested that a correlation existed between the degree of antimony susceptibility and the concentration of the moiety recognized by C219 in two clones. Binding of the C219 monoclonal antibody to the PGP-like component of was blocked by Pentostam, while the binding of C219 to multiple-drug resistant KB-V1 PGP was not inhibited by Pentostam, regardless of the PGP concentration. This suggests some degree of specificity in the binding of Pentostam to the PGP-like components. In addition, these studies have demonstrated that drug-sensitive accumulate two to five times more Sb-Pentostam than resistant clones.

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/content/journals/10.4269/ajtmh.1991.45.98
1991-07-01
2017-09-24
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