Source:http://linkedlifedata.com/resource/pubmed/id/18023288
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2008-1-14
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pubmed:abstractText |
Reactive oxygen species are well-known mediators of various biological responses. Recently, new homologues of the catalytic subunit of NADPH oxidase have been discovered in non-phagocytic cells. These new homologues (Nox1-Nox5) produce low levels of superoxides compared to the phagocytic homologue Nox2/gp91phox. Using Nox1 siRNA, we show that Nox1-dependent superoxide production affects the migration of HT29-D4 colonic adenocarcinoma cells on collagen-I. Nox1 inhibition or down-regulation led to a decrease of superoxide production and alpha 2 beta 1 integrin membrane availability. An addition of arachidonic acid stimulated Nox1-dependent superoxide production and HT29-D4 cell migration. Pharmacological evidences using phospholipase A2, lipoxygenases and protein kinase C inhibitors show that upstream regulation of Nox1 relies on arachidonic acid metabolism. Inhibition of 12-lipoxygenase decreased basal and arachidonic acid induced Nox1-dependent superoxide production and cell migration. Migration and ROS production inhibited by a 12-lipoxygenase inhibitor were restored by the addition of 12(S)-HETE, a downstream product of 12-lipoxygenase. Protein kinase C delta inhibition by rottlerin (and also GO6983) prevented Nox1-dependent superoxide production and inhibited cell migration, while other protein kinase C inhibitors were ineffective. We conclude that Nox1 activation by arachidonic acid metabolism occurs through 12-lipoxygenase and protein kinase C delta, and controls cell migration by affecting integrin alpha 2 subunit turn-over.
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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/Arachidonate 12-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha2beta1,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/NOX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-delta,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
1783
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
23-33
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18023288-Adenocarcinoma,
pubmed-meshheading:18023288-Arachidonate 12-Lipoxygenase,
pubmed-meshheading:18023288-Arachidonic Acids,
pubmed-meshheading:18023288-Cell Membrane,
pubmed-meshheading:18023288-Cell Movement,
pubmed-meshheading:18023288-Colonic Neoplasms,
pubmed-meshheading:18023288-HT29 Cells,
pubmed-meshheading:18023288-Humans,
pubmed-meshheading:18023288-Integrin alpha2beta1,
pubmed-meshheading:18023288-NADPH Oxidase,
pubmed-meshheading:18023288-Protein Kinase C-delta,
pubmed-meshheading:18023288-Superoxides
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pubmed:year |
2008
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pubmed:articleTitle |
Nox1-dependent superoxide production controls colon adenocarcinoma cell migration.
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pubmed:affiliation |
CNRS FRE 2737, Cytosquelette et Intégration des Signaux du Microenvironnement Tumoral, Aix-Marseille Université, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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