Macrophage paraoxonase 2 (PON2) expression is up-regulated by pomegranate juice phenolic anti-oxidants via PPARγ and AP-1 pathway activation
| Autor: | Michael Aviram, Maayan Shiner, Bianca Fuhrman |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Oxidative phosphorylation
medicine.disease_cause Antioxidants Cell Line Mice chemistry.chemical_compound Phenols Downregulation and upregulation Gallic Acid medicine Animals Gallic acid Transcription factor Punicalagin Flavonoids Lythraceae Microscopy Confocal biology Aryldialkylphosphatase Plant Extracts Chemistry Macrophages Paraoxonase Polyphenols food and beverages Molecular biology Hydrolyzable Tannins Up-Regulation PPAR gamma Transcription Factor AP-1 Oxidative Stress Biochemistry Polyphenol biology.protein Cardiology and Cardiovascular Medicine Oxidative stress Signal Transduction |
| Zdroj: | Atherosclerosis. 195:313-321 |
| ISSN: | 0021-9150 |
| Popis: | Paraoxonase 2 (PON2), a member of the paraoxonase gene family, was shown to protect macrophages against oxidative stress. Pomegranate juice (PJ), which contains potent polyphenol anti-oxidants, exhibits similar effects. We questioned possible association between PJ polyphenolics, macrophage oxidative stress, and cellular PON2 expression, in relation to the activation of specific PON2 transcription factors. Incubation of J774A.1 macrophages with PJ (0-50 microM of total polyphenols) dose-dependently increased expression (mRNA, protein) and activity and reduced macrophage oxidative status. These effects could be attributed to the PJ unique polyphenols, punicalagin and gallic acid. PJ polyphenol-induced up-regulation of PON2 was inhibited by 40% upon using the PPAR gamma inhibitor GW9662 (50 microM). Accordingly, the PPAR gamma ligand, rosiglitazone, dose-dependently stimulated macrophage PON2 expression, by up to 80%. Inhibition of AP-1 activation with SP600125, attenuated PJ-induced up-regulation of PON2 by 40%. Similarly, incubation of macrophages with PJ polyphenols in the presence of GW9662 or SP600125, significantly reduced their capacity to protect the cells against oxidative stress. We conclude that the anti-oxidative characteristics of PJ unique phenolics punicalagin and gallic acid could be related, at least in part, to their stimulatory effect on macrophage PON2 expression, a phenomenon which was shown to be associated with activation of the transcription factors PAPR gamma and AP-1. |
| Databáze: | OpenAIRE |
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