Linked Life Data

20621462

Source:http://linkedlifedata.com/resource/pubmed/id/20621462

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pubmed-article:20621462pubmed:abstractTextProtocatechuic acid (PCA) is a main metabolite of anthocyanins, whose daily intake is much higher than that of other polyphenols. PCA has biological effects, e.g., it induces the antioxidant/detoxifying enzyme gene expression. This study was aimed at defining the molecular mechanism responsible for PCA-induced over-expression of glutathione (GSH) peroxidase (GPx) and GSH reductase (GR) in J774 A.1 macrophages. New evidence is provided that PCA increases GPx and GR expression by inducing C-JUN NH(2)-terminal kinase (JNK)-mediated phosphorylation of Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2). RNA and proteins were extracted from cells treated with PCA (25 ?M) for different time points. Quantitative real-time polymerase chain reaction and immunoblotting analyses showed a rapid increase in mRNA (>60%) and protein (>50%) for both the enzymes. This was preceded by the up-regulation of Nrf2, in terms of mRNA and protein, and by its significant activation as assessed by increased Nrf2 phosphorylation and nuclear translocation (+60%). By using specific kinase inhibitors and detecting the activated form, we showed that JNK was the main upstream kinase responsible for Nrf2 activation. Convincing evidence is provided of a causal link between PCA-induced Nrf2 activation and increased enzyme expression. By silencing Nrf2 and using a JNK inhibitor, enzyme enhancement was counteracted. Finally, with the ChIP assay, we demonstrated that PCA-activated Nrf2 specifically bound ARE sequences in enzyme gene promoters. Our study demonstrates for the first time that PCA improves the macrophage endogenous antioxidant potential by a mechanism in which JNK-mediated Nrf2 activation plays an essential role. This knowledge could contribute to novel diet-based approaches aimed at counteracting oxidative injury by reinforcing endogenous defences.lld:pubmed
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pubmed-article:20621462pubmed:copyrightInfoCopyright © 2011 Elsevier Inc. All rights reserved.lld:pubmed
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pubmed-article:20621462pubmed:articleTitleProtocatechuic acid induces antioxidant/detoxifying enzyme expression through JNK-mediated Nrf2 activation in murine macrophages.lld:pubmed
pubmed-article:20621462pubmed:affiliationDepartment of Veterinary Public Health and Food Safety, Italian National Institute of Health, Rome, Italy.lld:pubmed
pubmed-article:20621462pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:20621462pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:20621462pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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