دورية أكاديمية
أعرض في EDS

The Agonist Action of Alkylphenols on TRPA1 Relates to Their Effects on Membrane Lipid Order: Implications for TRPA1-Mediated Chemosensation.

التفاصيل البيبلوغرافية
العنوان: The Agonist Action of Alkylphenols on TRPA1 Relates to Their Effects on Membrane Lipid Order: Implications for TRPA1-Mediated Chemosensation.
المؤلفون: Startek JB; Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.; VIB Center for Brain & Disease Research, 3000 Leuven, Belgium., Milici A; Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.; VIB Center for Brain & Disease Research, 3000 Leuven, Belgium., Naert R; Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.; VIB Center for Brain & Disease Research, 3000 Leuven, Belgium., Segal A; Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.; VIB Center for Brain & Disease Research, 3000 Leuven, Belgium., Alpizar YA; Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.; VIB Center for Brain & Disease Research, 3000 Leuven, Belgium., Voets T; Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.; VIB Center for Brain & Disease Research, 3000 Leuven, Belgium., Talavera K; Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.; VIB Center for Brain & Disease Research, 3000 Leuven, Belgium.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2021 Mar 25; Vol. 22 (7). Date of Electronic Publication: 2021 Mar 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Cell Membrane/*metabolism , Phenols/*pharmacology , TRPA1 Cation Channel/*agonists, Animals ; Anisotropy ; CHO Cells ; Calcium/metabolism ; Calcium Channels/metabolism ; Carbon/chemistry ; Cricetulus ; Dose-Response Relationship, Drug ; HEK293 Cells ; Humans ; Ligands ; Membrane Lipids ; Mice ; Nociceptors/metabolism ; Oxidative Stress
مستخلص: 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.
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معلومات مُعتمدة: G0D0417N and G0B2219N Fonds Wetenschappelijk Onderzoek; C14/18/086 Research Council KU Leuven
فهرسة مساهمة: Keywords: DPH; Laurdan; TRPA1; alkylphenols; mechanosensation; membrane fluidity
المشرفين على المادة: 0 (Calcium Channels)
0 (Ligands)
0 (Membrane Lipids)
0 (Phenols)
0 (TRPA1 Cation Channel)
0 (TRPA1 protein, human)
0 (Trpa1 protein, mouse)
7440-44-0 (Carbon)
SY7Q814VUP (Calcium)
تواريخ الأحداث: Date Created: 20210403 Date Completed: 20210611 Latest Revision: 20210611
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8037438
DOI: 10.3390/ijms22073368
PMID: 33806007
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms22073368