Title

Aspirin May Promote Mitochondrial Biogenesis Via The Production Of Hydrogen Peroxide And The Induction Of Sirtuin1/Pgc-1Α Genes

Keywords

Aryl hydrocarbon receptor; Dihydroxy benzoic acid; Mitochondria; Paraoxonase

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 (H2O 2), 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-1α (PGC-1α), 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 H 2O2, 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 O2-. and H2O2. As Sirt1 and PGC-1α profoundly affect mitochondrial metabolism and energy utilization, ASA may have therapeutic potential beyond its ability to inhibit cyclooxygenases. © 2012 Elsevier B.V. All rights reserved.

Publication Date

1-15-2013

Publication Title

European Journal of Pharmacology

Volume

699

Issue

1-3

Number of Pages

55-61

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.ejphar.2012.11.051

Socpus ID

84871862076 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84871862076

This document is currently not available here.

Share

COinS