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Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel

The TRPA1 channel is involved in a variety of physiological processes and its activation leads to pain perception and the development of inflammation. Peptide Ms 9a-1 from sea anemone Metridium senile is a positive modulator of TRPA1 and causes significant analgesic and anti-inflammatory effects by...

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Autores principales: Logashina, Yulia A., Lubova, Kseniya I., Maleeva, Ekaterina E., Palikov, Viktor A., Palikova, Yulia A., Dyachenko, Igor A., Andreev, Yaroslav A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320628/
https://www.ncbi.nlm.nih.gov/pubmed/35877758
http://dx.doi.org/10.3390/md20070465
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author Logashina, Yulia A.
Lubova, Kseniya I.
Maleeva, Ekaterina E.
Palikov, Viktor A.
Palikova, Yulia A.
Dyachenko, Igor A.
Andreev, Yaroslav A.
author_facet Logashina, Yulia A.
Lubova, Kseniya I.
Maleeva, Ekaterina E.
Palikov, Viktor A.
Palikova, Yulia A.
Dyachenko, Igor A.
Andreev, Yaroslav A.
author_sort Logashina, Yulia A.
collection PubMed
description The TRPA1 channel is involved in a variety of physiological processes and its activation leads to pain perception and the development of inflammation. Peptide Ms 9a-1 from sea anemone Metridium senile is a positive modulator of TRPA1 and causes significant analgesic and anti-inflammatory effects by desensitization of TRPA1-expressing sensory neurons. For structural and functional analysis of Ms 9a-1, we produced four peptides—Ms 9a-1 without C-terminal domain (abbreviated as N-Ms), short C-terminal domain Ms 9a-1 alone (C-Ms), and two homologous peptides (Ms 9a-2 and Ms 9a-3). All tested peptides possessed a reduced potentiating effect on TRPA1 compared to Ms 9a-1 in vitro. None of the peptides reproduced analgesic and anti-inflammatory properties of Ms 9a-1 in vivo. Peptides N-Ms and C-Ms were able to reduce pain induced by AITC (selective TRPA1 agonist) but did not decrease AITC-induced paw edema development. Fragments of Ms 9a-1 did not effectively reverse CFA-induced thermal hyperalgesia and paw edema. Ms 9a-2 and Ms 9a-3 possessed significant effects and anti-inflammatory properties in some doses, but their unexpected efficacy and bell-shape dose–responses support the hypothesis of other targets involved in their effects in vivo. Therefore, activity comparison of Ms 9a-1 fragments and homologues peptides revealed structural determinants important for TRPA1 modulation, as well as analgesic and anti-inflammatory properties of Ms9a-1.
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spelling pubmed-93206282022-07-27 Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel Logashina, Yulia A. Lubova, Kseniya I. Maleeva, Ekaterina E. Palikov, Viktor A. Palikova, Yulia A. Dyachenko, Igor A. Andreev, Yaroslav A. Mar Drugs Article The TRPA1 channel is involved in a variety of physiological processes and its activation leads to pain perception and the development of inflammation. Peptide Ms 9a-1 from sea anemone Metridium senile is a positive modulator of TRPA1 and causes significant analgesic and anti-inflammatory effects by desensitization of TRPA1-expressing sensory neurons. For structural and functional analysis of Ms 9a-1, we produced four peptides—Ms 9a-1 without C-terminal domain (abbreviated as N-Ms), short C-terminal domain Ms 9a-1 alone (C-Ms), and two homologous peptides (Ms 9a-2 and Ms 9a-3). All tested peptides possessed a reduced potentiating effect on TRPA1 compared to Ms 9a-1 in vitro. None of the peptides reproduced analgesic and anti-inflammatory properties of Ms 9a-1 in vivo. Peptides N-Ms and C-Ms were able to reduce pain induced by AITC (selective TRPA1 agonist) but did not decrease AITC-induced paw edema development. Fragments of Ms 9a-1 did not effectively reverse CFA-induced thermal hyperalgesia and paw edema. Ms 9a-2 and Ms 9a-3 possessed significant effects and anti-inflammatory properties in some doses, but their unexpected efficacy and bell-shape dose–responses support the hypothesis of other targets involved in their effects in vivo. Therefore, activity comparison of Ms 9a-1 fragments and homologues peptides revealed structural determinants important for TRPA1 modulation, as well as analgesic and anti-inflammatory properties of Ms9a-1. MDPI 2022-07-21 /pmc/articles/PMC9320628/ /pubmed/35877758 http://dx.doi.org/10.3390/md20070465 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Logashina, Yulia A.
Lubova, Kseniya I.
Maleeva, Ekaterina E.
Palikov, Viktor A.
Palikova, Yulia A.
Dyachenko, Igor A.
Andreev, Yaroslav A.
Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel
title Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel
title_full Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel
title_fullStr Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel
title_full_unstemmed Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel
title_short Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel
title_sort analysis of structural determinants of peptide ms 9a-1 essential for potentiating of trpa1 channel
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320628/
https://www.ncbi.nlm.nih.gov/pubmed/35877758
http://dx.doi.org/10.3390/md20070465
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