leukotriene-c4 and Leukemia

The ATP-dependent transport of the endogenous glutathione conjugate leukotriene C4 (LTC4) was more than 25-fold higher in membrane vesicles prepared from human leukemia cells (HL60/ADR) overexpressing the multidrug resistance-associated protein than from drug-sensitive parental HL60 cells or revertant cells. Similar results were obtained with S-(2,4-dinitrophenyl)glutathione as substrate. Photoaffinity labeling detected preferentially in the HL60/ADR membranes a 190-kilodalton protein binding [3H]LTC4 and 8-azido[alpha-32P]ATP. The [3H]LTC4-labeled 190-kilodalton protein was immunoprecipitated by an antiserum against the COOH-terminal sequence of multidrug resistance-associated protein. Our results indicate that multidrug resistance-associated protein mediates the ATP-dependent transport of LTC4 and structurally related anionic amphiphilic conjugates.

Topics: Adenosine Triphosphate; Amino Acid Sequence; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carrier Proteins; Cell Membrane; Humans; Leukemia; Leukotriene C4; Membrane Glycoproteins; Membrane Proteins; Molecular Sequence Data; Neoplasm Proteins; Peptide Fragments; Tumor Cells, Cultured; Vacuoles