Aspirin may influence cellular energy status

    Authors

    P. Kamble; D. Litvinov; C. A. Narasimhulu; X. T. Jiang;S. Parthasarathy

    Comments

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    Abbreviated Journal Title

    Eur. J. Pharmacol.

    Keywords

    ASA; Fatty acid oxidation; H2O2; Mitochondrial transcription factor A; MITOCHONDRIAL BIOGENESIS; MECHANISM; DISEASES; INHIBITION; METABOLISM; EXPRESSION; SIRTUINS; TARGETS; GENES; SIRT1; Pharmacology & Pharmacy

    Abstract

    In our previous findings, we have demonstrated that aspirin/acetyl salicylic acid (ASA) might induce sirtuins via aryl hydrocarbon receptor (Ah receptor). Induction effects included an increase in cellular paraoxonase 1 (PON1) activity and apolipoprotein A1 (ApoA1) gene expression. As predicted, ASA and salicylic acid (SA) treatment resulted in generation of H2O2, which is known to be an inducer of mitochondrial gene Sirt4 and other downstream target genes of Sirtl. Our current mass spectroscopic studies further confirm the metabolism of the drugs ASA and SA. Our studies show that HepG2 cells readily converted ASA to SA, which was then metabolized to 2,3-DHBA. HepG2 cells transfected with aryl hydrocarbon receptor siRNA upon treatment with SA showed the absence of a DHBA peak as measured by LC-MS/MS. MS studies for Sirtl action also showed a peak at 180.9 m/z for the deacetylated and chlorinated product formed from N-acetyl L epsilon-lysine, Thus an increase in Sirt4, Nrf2, Tfam, UCP1, eNOS, HO1 and STAT3 genes could profoundly affect mitochondrial function, cholesterol homeostasis, and fatty acid oxidation, suggesting that ASA could be beneficial beyond simply its ability to inhibit cyclooxygenase. (C) 2014 Elsevier B.V All rights reserved.

    Journal Title

    European Journal of Pharmacology

    Volume

    749

    Publication Date

    1-1-2015

    Document Type

    Article

    Language

    English

    First Page

    12

    Last Page

    19

    WOS Identifier

    WOS:000349761800002

    ISSN

    0014-2999

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