pubmed-article:20184376 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:20184376 | lifeskim:mentions | umls-concept:C0907532 | lld:lifeskim |
pubmed-article:20184376 | lifeskim:mentions | umls-concept:C1261381 | lld:lifeskim |
pubmed-article:20184376 | lifeskim:mentions | umls-concept:C1705165 | lld:lifeskim |
pubmed-article:20184376 | lifeskim:mentions | umls-concept:C0048897 | lld:lifeskim |
pubmed-article:20184376 | lifeskim:mentions | umls-concept:C0018966 | lld:lifeskim |
pubmed-article:20184376 | lifeskim:mentions | umls-concept:C1524081 | lld:lifeskim |
pubmed-article:20184376 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
pubmed-article:20184376 | lifeskim:mentions | umls-concept:C2700061 | lld:lifeskim |
pubmed-article:20184376 | lifeskim:mentions | umls-concept:C0136157 | lld:lifeskim |
pubmed-article:20184376 | pubmed:issue | 14 | lld:pubmed |
pubmed-article:20184376 | pubmed:dateCreated | 2010-4-6 | lld:pubmed |
pubmed-article:20184376 | pubmed:abstractText | Endothelial nitric oxide synthase (eNOS) is an important regulator of vascular and cardiac function. Peroxynitrite (ONOO(-)) inactivates eNOS, but questions remain regarding the mechanisms of this process. It has been reported that inactivation is due to oxidation of the eNOS zinc-thiolate cluster, rather than the cofactor tetrahydrobiopterin (BH(4)); however, this remains highly controversial. Therefore, we investigated the mechanisms of ONOO(-)-induced eNOS dysfunction and their dose dependence. Exposure of human eNOS to ONOO(-) resulted in a dose-dependent loss of activity with a marked destabilization of the eNOS dimer. HPLC analysis indicated that both free and eNOS-bound BH(4) were oxidized during exposure to ONOO(-); however, full oxidation of protein-bound biopterin required higher ONOO(-) levels. Additionally, ONOO(-) triggered changes in the UV/visible spectrum and heme content of the enzyme. Preincubation of eNOS with BH(4) decreased dimer destabilization and heme alteration. Addition of BH(4) to the ONOO(-)-destabilized eNOS dimer only partially rescued enzyme function. In contrast to ONOO(-) treatment, incubation with the zinc chelator TPEN with removal of enzyme-bound zinc did not change the eNOS activity or stability of the SDS-resistant eNOS dimer, demonstrating that the dimer stabilization induced by BH(4) does not require zinc occupancy of the zinc-thiolate cluster. While ONOO(-) treatment was observed to induce loss of Zn binding, this cannot account for the loss of enzyme activity. Therefore, ONOO(-)-induced eNOS inactivation is primarily due to oxidation of BH(4) and irreversible destruction of the heme/heme center. | lld:pubmed |
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pubmed-article:20184376 | pubmed:language | eng | lld:pubmed |
pubmed-article:20184376 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20184376 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:20184376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20184376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20184376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20184376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20184376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20184376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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pubmed-article:20184376 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:20184376 | pubmed:month | Apr | lld:pubmed |
pubmed-article:20184376 | pubmed:issn | 1520-4995 | lld:pubmed |
pubmed-article:20184376 | pubmed:author | pubmed-author:TsaiAh-LimAL | lld:pubmed |
pubmed-article:20184376 | pubmed:author | pubmed-author:BerkaVladimir... | lld:pubmed |
pubmed-article:20184376 | pubmed:author | pubmed-author:ZweierJay LJL | lld:pubmed |
pubmed-article:20184376 | pubmed:author | pubmed-author:HemannCraigC | lld:pubmed |
pubmed-article:20184376 | pubmed:author | pubmed-author:ChenWeiguoW | lld:pubmed |
pubmed-article:20184376 | pubmed:author | pubmed-author:ChenYeong-Ren... | lld:pubmed |