title: Aspirin may influence cellular energy status.
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 Sirt1. 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 Sirt1 action also showed a peak at 180.9 m/z for the deacetylated and chlorinated product formed from N-acetyl lε-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.
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, USA.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Kamble
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Litvinov
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, USA.
authors.forename: Chandrakala
authors.initials: C
authors.lastname: Aluganti Narasimhulu
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, USA.
authors.forename: Xueting
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, USA. Electronic address: spartha@ucf.edu.
authors.forename: Sampath
authors.initials: S
authors.lastname: Parthasarathy
mesh_terms: D016632:Apolipoprotein A-I / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics; D020156:Salicylic Acid / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000071256:Uncoupling Protein 1
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D004268:DNA-Binding Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C499631:TFAM protein, human; D014157:Transcription Factors; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D006861:Hydrogen Peroxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C525357:SIRT4 protein, human; D037761:Sirtuins; D020156:Salicylic Acid; D001241:Aspirin
keywords: ASA; Fatty acid oxidation; H(2)O(2); Mitochondrial transcription factor A