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Title: | The Agonist Action of Alkylphenols on TRPA1 Relates to Their Effects on Membrane Lipid Order: Implications for TRPA1-Mediated Chemosensation | Authors: | Startek, Justyna B. Milici, Alina Naert, Robbe Segal, Andrei AGUIAR ALPIZAR, Yeranddy Talavera, Karel Voets, Thomas |
Issue Date: | 2021 | Publisher: | MDPI | Source: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (7) (Art N° 3368) | Abstract: | The Transient Receptor Potential Ankyrin 1 cation channel (TRPA1) is a broadly-tuned chemosensor expressed in nociceptive neurons. Multiple TRPA1 agonists are chemically unrelated non-electrophilic compounds, for which the mechanisms of channel activation remain unknown. Here, we assess the hypothesis that such chemicals activate TRPA1 by inducing mechanical perturbations in the plasma membrane. We characterized the activation of mouse TRPA1 by non-electrophilic alkylphenols (APs) of different carbon chain lengths in the para position of the aromatic ring. Having discarded oxidative stress and the action of electrophilic mediators as activation mechanisms, we determined whether APs induce mechanical perturbations in the plasma membrane using dyes whose fluorescence properties change upon alteration of the lipid environment. APs activated TRPA1, with potency increasing with their lipophilicity. APs increased the generalized polarization of Laurdan fluorescence and the anisotropy of the fluorescence of 1,6-diphenyl-1,3,5-hexatriene (DPH), also according to their lipophilicity. Thus, the potency of APs for TRPA1 activation is an increasing function of their ability to induce lipid order and membrane rigidity. These results support the hypothesis that TRPA1 senses non-electrophilic compounds by detecting the mechanical alterations they produce in the plasma membrane. This may explain how structurally unrelated non-reactive compounds induce TRPA1 activation and support the role of TRPA1 as an unspecific sensor of potentially noxious compounds. | Notes: | Talavera, K (corresponding author), Katholieke Univ Leuven, Dept Cellular & Mol Med, Lab Ion Channel Res, B-3000 Leuven, Belgium.; Talavera, K (corresponding author), VIB Ctr Brain & Dis Res, B-3000 Leuven, Belgium. justyna.startek@kuleuven.be; milicialina13@gmail.com; robbe.naert@kuleuven.be; andrei.segal@kuleuven.be; yeranddy.aguiaralpizar@uhasselt.be; thomas.voets@kuleuven.be; karel.talavera@kuleuven.be |
Other: | Talavera, K (corresponding author), Katholieke Univ Leuven, Dept Cellular & Mol Med, Lab Ion Channel Res, B-3000 Leuven, Belgium ; VIB Ctr Brain & Dis Res, B-3000 Leuven, Belgium. justyna.startek@kuleuven.be; milicialina13@gmail.com; robbe.naert@kuleuven.be; andrei.segal@kuleuven.be; yeranddy.aguiaralpizar@uhasselt.be; thomas.voets@kuleuven.be; karel.talavera@kuleuven.be | Keywords: | TRPA1;alkylphenols;mechanosensation;membrane fluidity;Laurdan;DPH | Document URI: | http://hdl.handle.net/1942/34151 | ISSN: | 1661-6596 | e-ISSN: | 1422-0067 | DOI: | 10.3390/ijms22073368 | ISI #: | WOS:000638646700001 | Rights: | 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2022 |
Appears in Collections: | Research publications |
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ijms-22-03368 (1).pdf | Published version | 5.48 MB | Adobe PDF | View/Open |
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