| pubmed-article:15308628 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15308628 | lifeskim:mentions | umls-concept:C0014257 | lld:lifeskim |
| pubmed-article:15308628 | lifeskim:mentions | umls-concept:C1801960 | lld:lifeskim |
| pubmed-article:15308628 | lifeskim:mentions | umls-concept:C0079904 | lld:lifeskim |
| pubmed-article:15308628 | lifeskim:mentions | umls-concept:C0018270 | lld:lifeskim |
| pubmed-article:15308628 | lifeskim:mentions | umls-concept:C0024708 | lld:lifeskim |
| pubmed-article:15308628 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:15308628 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:15308628 | lifeskim:mentions | umls-concept:C1709305 | lld:lifeskim |
| pubmed-article:15308628 | pubmed:issue | 42 | lld:pubmed |
| pubmed-article:15308628 | pubmed:dateCreated | 2004-10-11 | lld:pubmed |
| pubmed-article:15308628 | pubmed:abstractText | The mitochondrial antioxidant manganese superoxide dismutase (Mn-SOD) plays a critical cytoprotective role against oxidative stress. Vascular endothelial growth factor (VEGF) was shown previously to induce expression of Mn-SOD in endothelial cells by a NADPH oxidase-dependent mechanism. The goal of the current study was to determine the transcriptional mechanisms underlying this phenomenon. VEGF resulted in protein kinase C-dependent phosphorylation of IkappaB and subsequent translocation of p65 NF-kappaB into the nucleus. Overexpression of constitutively active IkappaB blocked VEGF stimulation of Mn-SOD. In transient transfection assays, VEGF increased Mn-SOD promoter activity, an effect that was dependent on a second intronic NF-kappaB consensus motif. In contrast, VEGF-mediated induction of Mn-SOD was enhanced by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and by dominant negative Akt and was decreased by constitutively active Akt. Overexpression of a constitutively active (phosphorylation-resistant) form of FKHRL1 (TMFKHRL1) resulted in increased Mn-SOD expression, suggesting that the negative effect of PI3K-Akt involves attenuation of forkhead activity. In co-transfection assays, the Mn-SOD promoter was transactivated by TMFKHRL1. Flavoenzyme inhibitor, diphenyleneiodonium (DPI), and antisense oligonucleotides against p47phox (AS-p47phox) inhibited VEGF stimulation of IkappaB/NF-kappaB and forkhead phosphorylation, supporting a role for NADPH oxidase activity in both signaling pathways. Like VEGF, hepatocyte growth factor (HGF) activated the PI3K-Akt-forkhead pathway. However, HGF-PI3K-Akt-forkhead signaling was insensitive to diphenyleneiodonium and AS-p47phox. Moreover, HGF failed to induce phosphorylation of IkappaB/NF-kappaB or nuclear translocation of NF-kappaB and had no effect on Mn-SOD expression. Together, these data suggest that VEGF is uniquely coupled to Mn-SOD expression through growth factor-specific reactive oxygen species (ROS)-sensitive positive (protein kinase C-NF-kappaB) and negative (PI3K-Akt-forkhead) signaling pathways. | lld:pubmed |
| pubmed-article:15308628 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15308628 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15308628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15308628 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15308628 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:15308628 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:15308628 | pubmed:author | pubmed-author:AirdWilliam... | lld:pubmed |
| pubmed-article:15308628 | pubmed:author | pubmed-author:WuSheng-QianS... | lld:pubmed |
| pubmed-article:15308628 | pubmed:author | pubmed-author:AbidMd... | lld:pubmed |
| pubmed-article:15308628 | pubmed:author | pubmed-author:SchootsIvo... | lld:pubmed |
| pubmed-article:15308628 | pubmed:author | pubmed-author:SpokesKatheri... | lld:pubmed |
| pubmed-article:15308628 | pubmed:author | pubmed-author:MawhinneyChri... | lld:pubmed |
| pubmed-article:15308628 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15308628 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:15308628 | pubmed:volume | 279 | lld:pubmed |
| pubmed-article:15308628 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15308628 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15308628 | pubmed:pagination | 44030-8 | lld:pubmed |
| pubmed-article:15308628 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:meshHeading | pubmed-meshheading:15308628... | lld:pubmed |
| pubmed-article:15308628 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15308628 | pubmed:articleTitle | Vascular endothelial growth factor-mediated induction of manganese superoxide dismutase occurs through redox-dependent regulation of forkhead and IkappaB/NF-kappaB. | lld:pubmed |
| pubmed-article:15308628 | pubmed:affiliation | Division of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. rabid@bidmc.harvard.edu | lld:pubmed |
| pubmed-article:15308628 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15308628 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:15308628 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:4793 | entrezgene:pubmed | pubmed-article:15308628 | lld:entrezgene |
| entrez-gene:6648 | entrezgene:pubmed | pubmed-article:15308628 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:15308628 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:15308628 | lld:entrezgene |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15308628 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15308628 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15308628 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15308628 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15308628 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15308628 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15308628 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15308628 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15308628 | lld:pubmed |
