Omega-3 Fatty Acids Modulate TRPV4 Function through Plasma Membrane Remodeling
| Autor: | Francisco J. Sierra-Valdez, Valeria Vásquez, Herwig Joshua D, Julio F. Cordero-Morales, Jonathan R.M. Millet, Rebeca Caires, Esra Roan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
eicosapentaenoic acid Membrane Fluidity neurons Gene Expression TRPV Cation Channels Biology fatty acids Article General Biochemistry Genetics and Molecular Biology Cell Line Animals Genetically Modified 03 medical and health sciences 0302 clinical medicine Fatty Acids Omega-3 Metabolome Membrane fluidity Animals Humans Caenorhabditis elegans lcsh:QH301-705.5 Antihypertensive Agents Phospholipids chemistry.chemical_classification atomic force microscopy TRP channels Cell Membrane Endothelial Cells Fatty acid Lipid metabolism Metabolism Lipid Metabolism Phorbols Eicosapentaenoic acid 030104 developmental biology TRPV4 lcsh:Biology (General) Eicosanoid chemistry Biochemistry 17 18-epoxyeicosatetraenoic acid lipids (amino acids peptides and proteins) 030217 neurology & neurosurgery polyunsaturated fatty acids Polyunsaturated fatty acid |
| Zdroj: | Cell Rep Cell Reports, Vol 21, Iss 1, Pp 246-258 (2017) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2017.09.029 |
| Popis: | Dietary consumption of ω-3 polyunsaturated fatty acids (PUFAs), present in fish oils, is known to improve the vascular response, but their molecular targets remain largely unknown. Activation of the TRPV4 channel has been implicated in endothelium-dependent vasorelaxation. Here, we studied the contribution of ω-3 PUFAs to TRPV4 function by precisely manipulating the fatty acid content in Caenorhabditis elegans. By genetically depriving the worms of PUFAs, we determined that the metabolism of ω-3 fatty acids is required for TRPV4 activity. Functional, lipid metabolome, and biophysical analyses demonstrated that ω-3 PUFAs enhance TRPV4 function in human endothelial cells and support the hypothesis that lipid metabolism and membrane remodeling regulate cell reactivity. We propose a model whereby the eicosanoid’s epoxide group location increases membrane fluidity and influences the endothelial cell response by increasing TRPV4 channel activity. ω-3 PUFA-like molecules might be viable antihypertensive agents for targeting TRPV4 to reduce systemic blood pressure. |
| Databáze: | OpenAIRE |
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