Folic acid reverts dysfunction of endothelial nitric oxide synthase

作者: E. S. G. Stroes , E. E. van Faassen , M. Yo , P. Martasek , P. Boer

DOI: 10.1161/01.RES.86.11.1129

关键词: Nitric Oxide Synthase Type IIIEnosEndotheliumNitric oxideSuperoxideBiochemistryChemistryTetrahydrobiopterinEndothelial stem cellNitric oxide synthase

摘要: 5-methyltetrahydrofolate (MTHF), the active form of folic acid, has been reported to restore NO status in hypercholesterolemic patients. The mechanism this effect remains be established. We assessed effects L- and D-MTHF on tetrahydrobiopterin (BH(4))-free partially BH(4)-repleted endothelial synthase (eNOS). Superoxide production eNOS rate constants for trapping superoxide by MTHF were determined with electron paramagnetic resonance using 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO) as spin trap superoxide. was measured [(3)H]arginine-citrulline conversion or nitrite assay. scavenging similar, 1.4 x 10(4) ms(-1). In BH(4)-free eNOS, have no enzymatic activity. contrast, we observe a 2-fold First, is reduced. Second, enhanced. cultured cells, similar enhancement induced MTHF. present study, show direct activity both recombinant well which provides plausible explanation previously positive vivo.

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