Quercetin and Nf-kB / AP-1 induced apoptosis (Homo sapiens)

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1-4Cell membrane phospholipidsAP-1 transcription factor complexInflammationsmall MAFIncreases vasoconstrictionCOX1MAFKArachidonic acidFOSProstaglandin G2NFKB1ACOX2IKBKBQuercetinPhospholipase A2Prostaglandin H2MAFGNFKBIAPNFKBIAPNf-kBNOS1VEGFAAngiogenesisCarcinogenesisNFKB1JUNAP-1MMP1MetastasisAREROSInduces malformationInhibits dimerizationInhibits ubiquitinationDNA damageCYP2A6Carcinogenic metaboliteNFE2L2KEAP1NFE2L2NFE2L2Phase 2 enzymeProstaglandin I2Thromboxane A2Prostaglandin F2aProstaglandin D2Prostaglandin E2COX2Causes vasoconstriction; promotes platelet aggregationCauses vasodilation;inhibits platelet aggregationInduces vasoconstriction and secretion of IL-1 and IL-2E-boxGene boxE-boxGene box


Description

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.

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Bibliography

  1. Funk CD; ''Prostaglandins and leukotrienes: advances in eicosanoid biology.''; Science, 2001 PubMed Europe PMC Scholia
  2. Tanigawa S, Fujii M, Hou DX; ''Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin.''; Free Radic Biol Med, 2007 PubMed Europe PMC Scholia
  3. Ricciotti E, FitzGerald GA; ''Prostaglandins and inflammation.''; Arterioscler Thromb Vasc Biol, 2011 PubMed Europe PMC Scholia
  4. Ala Y. Issaa, Suresh R. Volatea, Michael J. Wargovich; ''The role of phytochemicals in inhibition of cancer and inflammation: New directions and perspectives''; Journal of Food Composition and Analysis, 2006 DOI Scholia

History

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CompareRevisionActionTimeUserComment
120750view12:32, 2 January 2022EweitzStraighten line
120749view12:31, 2 January 2022EweitzTighten graphics
120748view12:23, 2 January 2022EweitzUse gene symbols, refine graphics
120743view23:47, 27 December 2021EweitzModified title
119250view19:30, 22 June 2021FinterlyAdded DOI to PublicationXref
106204view12:10, 16 August 2019MaintBotHMDB identifier normalization
97772view13:34, 7 June 2018AMTanModified description
94228view08:53, 27 August 2017DeSlConnected which lines I could. There are some (from "gene box") where I do not know the meaning...
88907view08:51, 17 August 2016MirellaKalafatiOntology Term : 'regulatory pathway' added !
87626view08:54, 25 July 2016LindarieswijkOntology Term : 'apoptotic cell death pathway' added !
87375view09:56, 22 July 2016MaintBotadded missing graphids
80008view12:38, 30 April 2015Zariannotated small MAF
79692view20:20, 4 April 2015AlexanderPicoModified title
79583view08:35, 26 March 2015Zariadded ID for COX2 gene
72165view12:38, 25 October 2013Nuno
71259view21:20, 16 October 2013MaintBotAutomated update of data sources
62392view02:31, 28 April 2013AlexanderPicoRestored references
62391view02:26, 28 April 2013AlexanderPicoFixed datanodes, labels, lines and states
59177view18:43, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
57886view19:35, 4 February 2013MaintBotModified categories
56385view22:51, 6 January 2013Cboye21New pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACOX2GeneProductENSG00000168306 (Ensembl)
AngiogenesisPathwayWP1539 (WikiPathways)
Arachidonic acidMetaboliteHMDB0001043 (HMDB)
COX1GeneProduct4512 (Entrez Gene)
COX2GeneProduct5743 (Entrez Gene)
CYP2A6GeneProductENSG00000255974 (Ensembl) one of several possible phase 1 enzymes
CarcinogenesisPathway
Carcinogenic metaboliteMetabolite
DNA damagePathway
FOSGeneProductENSG00000170345 (Ensembl)
IKBKBGeneProductENSG00000104365 (Ensembl) Type your comment here
JUNGeneProductENSG00000177606 (Ensembl)
KEAP1GeneProductENSG00000079999 (Ensembl)
MAFGGeneProduct4097 (Entrez Gene)
MAFKGeneProduct7975 (Entrez Gene)
MMP1GeneProductENSG00000196611 (Ensembl)
MetastasisPathway
NFE2L2GeneProductENSG00000116044 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
NFKBIAProteinENSG00000100906 (Ensembl)
NOS1GeneProductENSG00000089250 (Ensembl)
Phase 2 enzyme Protein
Phospholipase A2GeneProduct3.1.1.4 (Enzyme Nomenclature)
Prostaglandin D2MetaboliteHMDB0001403 (HMDB)
Prostaglandin E2MetaboliteHMDB0001220 (HMDB)
Prostaglandin F2aMetaboliteHMDB0001139 (HMDB)
Prostaglandin G2MetaboliteHMDB0003235 (HMDB)
Prostaglandin H2MetaboliteHMDB0001381 (HMDB)
Prostaglandin I2MetaboliteHMDB0001335 (HMDB)
QuercetinMetaboliteHMDB0005794 (HMDB)
Thromboxane A2MetaboliteHMDB0001452 (HMDB)
VEGFAGeneProductENSG00000112715 (Ensembl)

Annotated Interactions

No annotated interactions

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