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Effects of cholesterol content on activity of P-glycoproteins and membrane physical state, and consequences for anthelmintic resistance in the nematode Haemonchus contortus
Eukaryote plasma membranes protect cells from chemical attack. Xenobiotics, taken up through passive diffusion, accumulate in the membranes, where they are captured by transporters, among which P-glycoproteins (Pgps). In nematodes such as Haemonchus contortus, eggshells and cuticles provide addition...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
EDP Sciences
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959138/ https://www.ncbi.nlm.nih.gov/pubmed/31934848 http://dx.doi.org/10.1051/parasite/2019079 |
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author | Riou, Mickaël Guégnard, Fabrice Le Vern, Yves Grasseau, Isabelle Koch, Christine Blesbois, Elisabeth Kerboeuf, Dominique |
author_facet | Riou, Mickaël Guégnard, Fabrice Le Vern, Yves Grasseau, Isabelle Koch, Christine Blesbois, Elisabeth Kerboeuf, Dominique |
author_sort | Riou, Mickaël |
collection | PubMed |
description | Eukaryote plasma membranes protect cells from chemical attack. Xenobiotics, taken up through passive diffusion, accumulate in the membranes, where they are captured by transporters, among which P-glycoproteins (Pgps). In nematodes such as Haemonchus contortus, eggshells and cuticles provide additional protective barriers against xenobiotics. Little is known about the role of these structures in the transport of chemical molecules. Pgps, members of the ABC transporter family, are present in eggshells and cuticles. Changes in the activity of these proteins have also been correlated with alterations in lipids, such as cholesterol content, in eggshells. However, the cellular mechanisms underlying these effects remain unclear. We show here that an experimental decrease in the cholesterol content of eggshells of Haemonchus contortus, with Methyl-beta-CycloDextrin (MβCD), results in an increase in membrane fluidity, favouring Pgp activity and leading to an increase in resistance to anthelmintics. This effect is modulated by the initial degree of anthelminthic resistance of the eggs. These results suggest that eggshell fluidity plays a major role in the modulation of Pgp activity. They confirm that Pgp activity is highly influenced by the local microenvironment, in particular sterols, as observed in some vertebrate models. Thus, eggshell barriers could play an active role in the transport of xenobiotics. |
format | Online Article Text |
id | pubmed-6959138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | EDP Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-69591382020-01-17 Effects of cholesterol content on activity of P-glycoproteins and membrane physical state, and consequences for anthelmintic resistance in the nematode Haemonchus contortus Riou, Mickaël Guégnard, Fabrice Le Vern, Yves Grasseau, Isabelle Koch, Christine Blesbois, Elisabeth Kerboeuf, Dominique Parasite Research Article Eukaryote plasma membranes protect cells from chemical attack. Xenobiotics, taken up through passive diffusion, accumulate in the membranes, where they are captured by transporters, among which P-glycoproteins (Pgps). In nematodes such as Haemonchus contortus, eggshells and cuticles provide additional protective barriers against xenobiotics. Little is known about the role of these structures in the transport of chemical molecules. Pgps, members of the ABC transporter family, are present in eggshells and cuticles. Changes in the activity of these proteins have also been correlated with alterations in lipids, such as cholesterol content, in eggshells. However, the cellular mechanisms underlying these effects remain unclear. We show here that an experimental decrease in the cholesterol content of eggshells of Haemonchus contortus, with Methyl-beta-CycloDextrin (MβCD), results in an increase in membrane fluidity, favouring Pgp activity and leading to an increase in resistance to anthelmintics. This effect is modulated by the initial degree of anthelminthic resistance of the eggs. These results suggest that eggshell fluidity plays a major role in the modulation of Pgp activity. They confirm that Pgp activity is highly influenced by the local microenvironment, in particular sterols, as observed in some vertebrate models. Thus, eggshell barriers could play an active role in the transport of xenobiotics. EDP Sciences 2020-01-14 /pmc/articles/PMC6959138/ /pubmed/31934848 http://dx.doi.org/10.1051/parasite/2019079 Text en © M. Riou et al., published by EDP Sciences, 2020 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Riou, Mickaël Guégnard, Fabrice Le Vern, Yves Grasseau, Isabelle Koch, Christine Blesbois, Elisabeth Kerboeuf, Dominique Effects of cholesterol content on activity of P-glycoproteins and membrane physical state, and consequences for anthelmintic resistance in the nematode Haemonchus contortus |
title | Effects of cholesterol content on activity of P-glycoproteins and membrane physical state, and consequences for anthelmintic resistance in the nematode Haemonchus contortus |
title_full | Effects of cholesterol content on activity of P-glycoproteins and membrane physical state, and consequences for anthelmintic resistance in the nematode Haemonchus contortus |
title_fullStr | Effects of cholesterol content on activity of P-glycoproteins and membrane physical state, and consequences for anthelmintic resistance in the nematode Haemonchus contortus |
title_full_unstemmed | Effects of cholesterol content on activity of P-glycoproteins and membrane physical state, and consequences for anthelmintic resistance in the nematode Haemonchus contortus |
title_short | Effects of cholesterol content on activity of P-glycoproteins and membrane physical state, and consequences for anthelmintic resistance in the nematode Haemonchus contortus |
title_sort | effects of cholesterol content on activity of p-glycoproteins and membrane physical state, and consequences for anthelmintic resistance in the nematode haemonchus contortus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959138/ https://www.ncbi.nlm.nih.gov/pubmed/31934848 http://dx.doi.org/10.1051/parasite/2019079 |
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