1. Drug resistance is affected by colocalization of P-glycoproteins in raft-like structures unexpected in eggshells of the nematode Haemonchus contortus
- Author
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Pierre-Yves Sizaret, Mickaël Riou, Yves Le Vern, D. Kerboeuf, Fabrice Guégnard, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Infectiologie Animale et Santé Publique (UR IASP), and Inconnu
- Subjects
Membrane Fluidity ,[SDV]Life Sciences [q-bio] ,Drug Resistance ,Biological Transport, Active ,ATP-binding cassette transporter ,Xenobiotic transport ,Drug resistance ,Biochemistry ,030308 mycology & parasitology ,03 medical and health sciences ,Membrane Microdomains ,Botany ,Animals ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,P-glycoprotein ,Ovum ,chemistry.chemical_classification ,0303 health sciences ,biology ,Colocalization ,Cell Biology ,biology.organism_classification ,Flow Cytometry ,3. Good health ,Cell biology ,Nematode ,chemistry ,Microscopy, Fluorescence ,biology.protein ,Haemonchus ,Glycoprotein ,Haemonchus contortus - Abstract
In nematodes as in other eukaryotes, there is increasing evidence that drug resistance depends on both changes in the drug cellular targets and in nonspecific mechanisms, involving cellular detoxification by efflux pumps. In vertebrates, P-glycoproteins (Pgp) are membrane efflux pumps responsible for the elimination of xenobiotic agents, especially drugs. We previously reported the presence of Pgp pumps in eggshells and cuticles of the nematode Haemonchus contortus. Eggshells and cuticles are different from cell membranes, in particular they include a chitin layer. Nevertheless these structures present some common biological features with cell membranes and play a role in xenobiotic transport. Pgp activity has been shown to depend on the lipid environment and, in particular, on the cholesterol content in both vertebrate and nematode models. In vertebrates, Pgp is in part located in membrane cholesterol-enriched microdomains, the rafts. We describe here, for the first time, lipid microdomains in eggshells that could correspond with raft-like structures (RLSs). Moreover, a large proportion of the Pgp was shown to colocalize with these RLSs. The functional consequences of the colocalization for xenobiotic transport and thus drug resistance in nematodes were analyzed and compared with results obtained in vertebrates. An understanding of such mechanisms is crucial in overcoming the failure of drug treatments due to the development of resistance.
- Published
- 2010