Title
Aspirin may promote mitochondrial biogenesis via the production of hydrogen peroxide and the induction of Sirtuin1/PGC-1 alpha genes
Abbreviated Journal Title
Eur. J. Pharmacol.
Keywords
Aryl hydrocarbon receptor; Dihydroxy benzoic acid; Mitochondria; Paraoxonase; ACETYLSALICYLIC-ACID; SIRT1; DEACETYLASE; INHIBITION; MOUSE; CELLS; ATHEROSCLEROSIS; RESVERATROL; PGC-1-ALPHA; SUPEROXIDE; Pharmacology & Pharmacy
Abstract
Based on the rapid hydrolysis of acetyl salicylic acid (ASA, Aspirin) to salicylic acid (SA), the ability of SA to form dihydroxy benzoic acid (DBA), and the latter's redox reactions to yield hydrogen peroxide (H2O2), we predicted that ASA may have the potential to induce Sirtuin1 (Sirt1) and its downstream effects. We observed that treatment of cultured liver cells with ASA resulted in the induction of Sirt1, peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1 alpha), and NAD(P)H quinone oxidoreductase 1 (Nqo1) genes. Paraoxonase 1 (PON1) and Aryl hydrocarbon receptor (AhR) siRNA transfections inhibited the induction of gene expressions by ASA suggesting the need for the acetyl ester hydrolysis and hydroxylation to DHBA. The latter also induced Sirt1, confirming the proposed pathway. As predicted, ASA and SA treatment resulted in the production of H2O2, a known inducer of Sirt1 and confirmed in the current studies. More importantly, ASA treatment resulted in an increase in mitochondria as seen by tracking dyes. We suggest that DHBA, generated from ASA, via its oxidation/reduction reactions mediated by Nqo1 might be involved in the production of O-2(-center dot) and H2O2. As Sirt1 and PGC-1 alpha profoundly affect mitochondrial metabolism and energy utilization, ASA may have therapeutic potential beyond its ability to inhibit cyclooxygenases. (C) 2012 Elsevier B.V. All rights reserved.
Journal Title
European Journal of Pharmacology
Volume
699
Issue/Number
1-3
Publication Date
1-1-2013
Document Type
Article
Language
English
First Page
55
Last Page
61
WOS Identifier
ISSN
0014-2999
Recommended Citation
"Aspirin may promote mitochondrial biogenesis via the production of hydrogen peroxide and the induction of Sirtuin1/PGC-1 alpha genes" (2013). Faculty Bibliography 2010s. 4180.
https://stars.library.ucf.edu/facultybib2010/4180
Comments
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