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Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway

Neuropathic pain is a chronic painful disease. Data have shown that reactive oxygen species (ROS) are implicated in chronic pain. Particularly, the enhanced ROS production alters the mitochondrial genome and proteome through the accumulation of lipid peroxidation products, such as 4-hydroxynonenal (...

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Autores principales: Ilari, Sara, Giancotti, Luigino Antonio, Lauro, Filomena, Gliozzi, Micaela, Malafoglia, Valentina, Palma, Ernesto, Tafani, Marco, Russo, Matteo Antonio, Tomino, Carlo, Fini, Massimo, Salvemini, Daniela, Mollace, Vincenzo, Muscoli, Carolina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698145/
https://www.ncbi.nlm.nih.gov/pubmed/33182469
http://dx.doi.org/10.3390/antiox9111103
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author Ilari, Sara
Giancotti, Luigino Antonio
Lauro, Filomena
Gliozzi, Micaela
Malafoglia, Valentina
Palma, Ernesto
Tafani, Marco
Russo, Matteo Antonio
Tomino, Carlo
Fini, Massimo
Salvemini, Daniela
Mollace, Vincenzo
Muscoli, Carolina
author_facet Ilari, Sara
Giancotti, Luigino Antonio
Lauro, Filomena
Gliozzi, Micaela
Malafoglia, Valentina
Palma, Ernesto
Tafani, Marco
Russo, Matteo Antonio
Tomino, Carlo
Fini, Massimo
Salvemini, Daniela
Mollace, Vincenzo
Muscoli, Carolina
author_sort Ilari, Sara
collection PubMed
description Neuropathic pain is a chronic painful disease. Data have shown that reactive oxygen species (ROS) are implicated in chronic pain. Particularly, the enhanced ROS production alters the mitochondrial genome and proteome through the accumulation of lipid peroxidation products, such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). Sirtuin 3 (SIRT3) is a mitochondrial protein and its activity can reduce ROS levels by modulating key antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Here, we evaluated the role of SIRT3 in the maintenance of basal levels of ROS in a model of chronic constriction injury (CCI) of the sciatic nerve and the protective effects of a natural antioxidant, the bergamot polyphenolic fraction (BPF). Rats were exposed to CCI of the sciatic nerve in the presence or absence of BPF (25–75 mg/kg). Level of acetylation, post-translational modulation on cysteine residues of proteins by HNE and SIRT3 activation, were detected in the spinal cord through western blotting, WES methodology and enzymatic assays. Our results reported that SIRT3 carbonylation and therefore its inactivation contributes to mitochondrial MnSOD hyperacetylation during CCI induced neuropathic pain in rats. In particular, we have demonstrated a close relation between oxidative stress, hyperalgesia, allodynia and sirtuins inactivation reverted by BPF administration.
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spelling pubmed-76981452020-11-29 Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway Ilari, Sara Giancotti, Luigino Antonio Lauro, Filomena Gliozzi, Micaela Malafoglia, Valentina Palma, Ernesto Tafani, Marco Russo, Matteo Antonio Tomino, Carlo Fini, Massimo Salvemini, Daniela Mollace, Vincenzo Muscoli, Carolina Antioxidants (Basel) Article Neuropathic pain is a chronic painful disease. Data have shown that reactive oxygen species (ROS) are implicated in chronic pain. Particularly, the enhanced ROS production alters the mitochondrial genome and proteome through the accumulation of lipid peroxidation products, such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). Sirtuin 3 (SIRT3) is a mitochondrial protein and its activity can reduce ROS levels by modulating key antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Here, we evaluated the role of SIRT3 in the maintenance of basal levels of ROS in a model of chronic constriction injury (CCI) of the sciatic nerve and the protective effects of a natural antioxidant, the bergamot polyphenolic fraction (BPF). Rats were exposed to CCI of the sciatic nerve in the presence or absence of BPF (25–75 mg/kg). Level of acetylation, post-translational modulation on cysteine residues of proteins by HNE and SIRT3 activation, were detected in the spinal cord through western blotting, WES methodology and enzymatic assays. Our results reported that SIRT3 carbonylation and therefore its inactivation contributes to mitochondrial MnSOD hyperacetylation during CCI induced neuropathic pain in rats. In particular, we have demonstrated a close relation between oxidative stress, hyperalgesia, allodynia and sirtuins inactivation reverted by BPF administration. MDPI 2020-11-09 /pmc/articles/PMC7698145/ /pubmed/33182469 http://dx.doi.org/10.3390/antiox9111103 Text en © 2020 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ilari, Sara
Giancotti, Luigino Antonio
Lauro, Filomena
Gliozzi, Micaela
Malafoglia, Valentina
Palma, Ernesto
Tafani, Marco
Russo, Matteo Antonio
Tomino, Carlo
Fini, Massimo
Salvemini, Daniela
Mollace, Vincenzo
Muscoli, Carolina
Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway
title Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway
title_full Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway
title_fullStr Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway
title_full_unstemmed Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway
title_short Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway
title_sort natural antioxidant control of neuropathic pain—exploring the role of mitochondrial sirt3 pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698145/
https://www.ncbi.nlm.nih.gov/pubmed/33182469
http://dx.doi.org/10.3390/antiox9111103
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