Source:http://linkedlifedata.com/resource/pubmed/id/20621462
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2011-4-18
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| pubmed:abstractText |
Protocatechuic 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.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Reductase,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxybenzoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-E2-Related Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Nfe2l2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/protocatechuic acid
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1873-4847
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
22
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
409-17
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| pubmed:meshHeading |
pubmed-meshheading:20621462-Animals,
pubmed-meshheading:20621462-Antioxidants,
pubmed-meshheading:20621462-Cell Line,
pubmed-meshheading:20621462-Cell Nucleus,
pubmed-meshheading:20621462-Chromatin,
pubmed-meshheading:20621462-Gene Silencing,
pubmed-meshheading:20621462-Glutathione Peroxidase,
pubmed-meshheading:20621462-Glutathione Reductase,
pubmed-meshheading:20621462-Hydroxybenzoic Acids,
pubmed-meshheading:20621462-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:20621462-Macrophages,
pubmed-meshheading:20621462-Metabolic Detoxication, Drug,
pubmed-meshheading:20621462-Mice,
pubmed-meshheading:20621462-NF-E2-Related Factor 2,
pubmed-meshheading:20621462-Oxidation-Reduction,
pubmed-meshheading:20621462-Phosphorylation,
pubmed-meshheading:20621462-Protein Kinase Inhibitors,
pubmed-meshheading:20621462-RNA, Small Interfering,
pubmed-meshheading:20621462-Reactive Oxygen Species,
pubmed-meshheading:20621462-Up-Regulation
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| pubmed:year |
2011
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| pubmed:articleTitle |
Protocatechuic acid induces antioxidant/detoxifying enzyme expression through JNK-mediated Nrf2 activation in murine macrophages.
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| pubmed:affiliation |
Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Rome, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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