Disease relevance of p-glycoprotein

• Identification and stage-specific expression of two putative P-glycoprotein coding genes in Onchocerca volvulus [1].

High impact information on p-glycoprotein

• By transposon-mediated deletion mutagenesis we generated nematode strains with deleted P-glycoprotein genes and found that the pgp-3 deletion mutant, but not the pgp-1 mutant, is sensitive to both colchicine and chloroquine [2].
• Quantitative analysis of pgp mRNA levels during development showed that pgp-1, -2, and -3 were expressed throughout the life cycle of C.elegans, albeit with some variation indicating developmental regulation [3].
• Genomic organization and effects of ivermectin selection on Onchocerca volvulus P-glycoprotein [4].
• However, the P-glycoprotein alleles, in the worms from the patients under treatment were not in Hardy-Weinberg equilibrium, and analysis of the allele frequencies of beta-tubulin suggested that this gene may have also been under selection in the worms from the ivermectin-treated patients [5].
• In order to find the homologues of P-gp in O. volvulus, reverse transcription polymerase chain reaction (RT-PCR) has been performed in a specially synthesized cDNA pool and two full-length cDNAs have been cloned and sequenced [1].

Biological context of p-glycoprotein

• Furthermore, the current knowledge on the role of Pgp in molecular mechanisms of drug resistance in the parasitic protozoan genus Trypanosoma is discussed [6].
• The implication of the glycosylation of Pgp in the activity and/or degradation of these pumps in eukaryotic cells is discussed [7].

Anatomical context of p-glycoprotein

• The cell-membrane efflux pump, P-glycoprotein (Pgp), appears to contribute to anthelmintic resistance [6].
• The delayed intestinal transit time caused by LPM and a potential competition between MXD and LPM for the P-glycoprotein-mediated bile/intestinal secretion processes, may account for the enhanced MXD systemic availability measured in cattle in the current work [8].

Associations of p-glycoprotein with chemical compounds

• Concentration-response curves for the toxicants arsenite and aldicarb, both of which affect motility, were determined for wild-type and several mutant strains, identifying P-glycoprotein mutants as not significantly more sensitive to either compound, while cat-4 mutants are more sensitive to arsenite but not aldicarb [9].

Analytical, diagnostic and therapeutic context of p-glycoprotein

• The molecule largely eludes P glycoprotein-mediated drug efflux, and an analog is currently being evaluated in clinical trials as cancer chemotherapy [10].
• Northern blotting showed that P-glycoprotein genes are transcribed in a developmentally regulated fashion in Haemonchus contortus [11].

References