Cargando…
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 (...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783615762535022592 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7698145 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT ilarisara naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT giancottiluiginoantonio naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT laurofilomena naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT gliozzimicaela naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT malafogliavalentina naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT palmaernesto naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT tafanimarco naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT russomatteoantonio naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT tominocarlo naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT finimassimo naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT salveminidaniela naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT mollacevincenzo naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway AT muscolicarolina naturalantioxidantcontrolofneuropathicpainexploringtheroleofmitochondrialsirt3pathway |