Premium
Modulation of sirtuins during acute inflammatory pain: the role of ROS
Author(s) -
Muscoli Carolina,
Lauro Filomena,
Ilari Sara,
Pucci Bruna,
Dagostino Concetta,
Gliozzi Micaela,
Tafani Marco,
Palma Ernesto,
Ventrice Domenica,
Russo Matteo,
Fini Massimo,
Mollace Vincenzo,
Salvemini Daniela
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.887.6
Subject(s) - oxidative stress , chemistry , inflammation , reactive oxygen species , sirt3 , nitrotyrosine , lipid peroxidation , peroxynitrite , antioxidant , pharmacology , sirtuin , biochemistry , microbiology and biotechnology , medicine , superoxide , nad+ kinase , biology , enzyme , nitric oxide synthase
Free radicals plays a crucial role in the enhanced pain sensitivity experienced during inflammatory diseases. ROS accumulation modifies the activity of sirtuins (SIRT 1–7), proteins that deacetylate histones and non‐histone proteins playing an important role in regulation of inflammation and neurodegenerative diseases. SIRT1 either directly or indirectly influences the redox property of the cell and it is also regulated by oxidative stress. SIRT3 plays a role in the maintenance of basal levels of reactive oxygen species; it stimulates MnSOD and catalase production by FOXO activation as SIRT1 and deacetylates two critical lysine residues on MnSOD itself to promote its antioxidative activity. We show that removal of free radicals by antioxidants is able to block the thermal hyperalgia in the carrageenan‐induced inflammation model. This effect was associated with inhibition of edema, lipid peroxidation, nitrotyrosine formation and PARP activation in the paw exudates and to nitrotyrosine formation in the spinal cord. We report that SIRT1 and SIRT3 are decreased in the spinal cord of carrageenan treated rats and that removal of free radicals by antioxidant enhanced their expression. These findings demonstrate for the first time that sirtuins activation by antioxidants is beneficial during oxidative stress induced hyperalgesia and inflammation. This work has been supported by PON a3–00359 and GR‐2010–2318370