Quercetin and Nf-kB / AP-1 induced apoptosis (WP2435)
Homo sapiens
Quercetin is a flavonoid that is widely distributed in nature. In this pathway, its dual nature is depicted. On the one hand, it is capable of exerting anti-oxidant and anti-inflammatory effects by inhibiting the PLA2-induced conversion of cell membrane phospholipids to arachidonic acid, reducing the downstream synthesis of pro-inflammatory prostaglandins; furthermore, inhibition of NF-kB and AP-1 transcription factor activation also contribute to these effects. On the other hand, quercetin itself may - paraxodically - generate ROS, as well as facilitate the activation of NFE2L2, which results in the production of CYP2A6. This isotype of CYP450 was found to be involved in the formation of carcinogenic metabolites. Both of these effects culminate in DNA damage. It has been observed, however, that these pro-oxidant effects are dominant at higher concentrations, whereas anti-oxidant effects are dominant at lower concentrations. Based on this, it has been suggested that quercetin may have a scavenging effect.
Authors
Chris Boye , Alex Pico , Nuno , Zahra Roudbari , Linda Rieswijk , Marianthi Kalafati , Denise Slenter , Andika Tan , Finterly Hu , Eric Weitz , and Egon WillighagenActivity
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
regulatory pathway apoptotic cell death pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| Prostaglandin G2 | Metabolite | hmdb:HMDB0003235 | |
| Quercetin | Metabolite | hmdb:HMDB0005794 | |
| Prostaglandin H2 | Metabolite | hmdb:HMDB0001381 | |
| Arachidonic acid | Metabolite | hmdb:HMDB0001043 | |
| Prostaglandin I2 | Metabolite | hmdb:HMDB0001335 | |
| Thromboxane A2 | Metabolite | hmdb:HMDB0001452 | |
| Prostaglandin F2a | Metabolite | hmdb:HMDB0001139 | |
| Prostaglandin D2 | Metabolite | hmdb:HMDB0001403 | |
| Prostaglandin E2 | Metabolite | hmdb:HMDB0001220 | |
| COX1 | GeneProduct | ncbigene:4512 | |
| IKBKB | GeneProduct | ensembl:ENSG00000104365 | |
| NFKB1 | GeneProduct | ensembl:ENSG00000109320 | |
| MAFK | GeneProduct | ncbigene:7975 | |
| Phospholipase A2 | GeneProduct | eccode:3.1.1.4 | |
| MAFG | GeneProduct | ncbigene:4097 | |
| ACOX2 | GeneProduct | ensembl:ENSG00000168306 | |
| NFKBIA | GeneProduct | ensembl:ENSG00000100906 | |
| FOS | GeneProduct | ensembl:ENSG00000170345 | |
| NOS1 | GeneProduct | ensembl:ENSG00000089250 | |
| VEGFA | GeneProduct | ensembl:ENSG00000112715 | |
| JUN | GeneProduct | ensembl:ENSG00000177606 | |
| MMP1 | GeneProduct | ensembl:ENSG00000196611 | |
| CYP2A6 | GeneProduct | ensembl:ENSG00000255974 | one of several possible phase 1 enzymes |
| NFE2L2 | GeneProduct | ensembl:ENSG00000116044 | |
| KEAP1 | GeneProduct | ensembl:ENSG00000079999 | |
| COX2 | GeneProduct | ncbigene:5743 | |
| NFKBIA | Protein | ensembl:ENSG00000100906 |
References
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- Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Tanigawa S, Fujii M, Hou DX. Free Radic Biol Med. 2007 Jun 1;42(11):1690–703. PubMed Europe PMC Scholia
- Prostaglandins and inflammation. Ricciotti E, FitzGerald GA. Arterioscler Thromb Vasc Biol. 2011 May;31(5):986–1000. PubMed Europe PMC Scholia