{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:55:15Z","timestamp":1791921315183,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,1,7]],"date-time":"2008-01-07T00:00:00Z","timestamp":1199664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hyperhomocysteinemia (HHcy) is associated with atherosclerotic events involving the modulation of arachidonic acid (AA) metabolism and the activation of matrix metalloproteinase\u20109 (MMP\u20109). Cytochrome P450 (CYP) epoxygenase\u20102J2 (CYP2J2) is abundant in the heart endothelium, and its AA metabolites epoxyeicosatrienoic acids (EETs) mitigates inflammation through NF\u2010\u03ba\u03b2. However, the underlying molecular mechanisms for MMP\u20109 regulation by CYP2J2 in HHcy remain obscure. We sought to determine the molecular mechanisms by which P450 epoxygenase gene transfection or EETs supplementation attenuate homocysteine (Hcy)\u2010induced MMP\u20109 activation. CYP2J2 was over\u2010expressed in mouse aortic endothelial cells (MAECs) by transfection with the pcDNA3.1\/CYP2J2 vector. The effects of P450 epoxygenase transfection or exogenous supplementation of EETs on NF\u2010\u03ba\u03b2\u2010mediated MMP\u20109 regulation were evaluated using Western blot, in\u2010gel gelatin zymography, electromobility shift assay, immunocytochemistry. The result suggested that Hcy downregulated CYP2J2 protein expression and dephosphorylated PI3K\u2010dependent AKT signal. Hcy induced the nuclear translocation of NF\u2010\u03ba\u03b2 via downregulation of IK\u03b2\u03b1 (endogenous cytoplasmic inhibitor of NF\u2010\u03ba\u03b2). Hcy induced MMP\u20109 activation by increasing NF\u2010\u03ba\u03b2\u2013DNA binding. Moreover, P450 epoxygenase transfection or exogenous addition of 8,9\u2010EET phosphorylated the AKT and attenuated Hcy\u2010induced MMP\u20109 activation. This occurred, in part, by the inhibition of NF\u2010\u03ba\u03b2 nuclear translocation, NF\u2010\u03ba\u03b2\u2013DNA binding and activation of IK\u03b2\u03b1. The study unequivocally suggested the pivotal role of EETs in the modulation of Hcy\/MMP\u20109 signal. J. Cell. Physiol. 215: 771\u2013781, 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21356","type":"journal-article","created":{"date-parts":[[2008,1,7]],"date-time":"2008-01-07T22:17:06Z","timestamp":1199744226000},"page":"771-781","source":"Crossref","is-referenced-by-count":45,"title":["Cytochrome P450 (CYP) 2J2 gene transfection attenuates MMP\u20109 via inhibition of NF\u2010\u03ba\u03b2 in hyperhomocysteinemia"],"prefix":"10.1002","volume":"215","author":[{"given":"Karni S.","family":"Moshal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl C.","family":"Zeldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas D.","family":"Sithu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utpal","family":"Sen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neetu","family":"Tyagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munish","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"William M.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naira","family":"Metreveli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothea S.E.","family":"Rosenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahavir","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Vacek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter E.","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeagbo","family":"Ayotunde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh C.","family":"Tyagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,1,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh1501.094396"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"15334","DOI":"10.1016\/S0021-9258(18)66872-3","article-title":"Inhibition of cyclo\u2010oxygenase activity and platelet aggregation by epoxyeicosatrienoic acids. 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