Role of nitrogen oxides on eicosanoid production during atherosclerosis: understanding the controversies.
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Arteriosclerosis↗
Biomedical subjects
R K Upmacis
Publications and source records attributed to R K Upmacis.
Regulation of prostaglandin H2 synthase activity by nitrogen oxides.
Nitric oxide and its derivatives have been shown to both activate and inhibit prostaglandin H(2) synthase 1 (PGHS-1). We set out to determine the mechanisms by which different nitrogen oxide derivatives modulate PGHS-1 activity. To this end, we show that 3-morpholinosydnonimine hydrochloride (SIN-1), a compound capable of generating peroxynitrite, activates purified PGHS-1 and also stimulates PGE(2) production in arterial smooth muscle cells in the presence of exogenous arachidonic acid. The effect of SIN-1 in smooth muscle cells was abrogated by superoxide and peroxynitrite inhibitors, which supports the hypothesis that peroxynitrite is an activating species of PGHS-1. Indeed, authentic peroxynitrite also induced PGE(2) production in arachidonic acid-stimulated cells. In contrast, when cells were exposed to the nitric oxide-releasing compound 1-hydroxy-2-oxo-3-[(methylamino)propyl]-3-methyl-1-triazene (NOC-7), PGHS-1 enzyme activity was inhibited in the presence of exogenous arachidonic acid. Finally, in lipid-loaded smooth muscle cells, we demonstrate that SIN-1 stimulates arachidonic acid-induced PGE(2) production; albeit, the extent of activation is reduced compared to that under normal conditions. These results indicate that formation of peroxynitrite is a key intermediary step in PGHS-1 activation. However, other forms of NO(x)() inhibit PGHS-1. These results may have implications in the regulation of vascular function and tone in normal and atherosclerotic arteries.
Animals↗
Long-range electron transfer in myoglobin.
The distance and driving-force dependences of electron transfer (ET) in a set of four surface-ruthenated myoglobins, in which the heme prosthetic group has been systematically replaced by a series of metalloporphyrins of differing excited-state redox potentials, have provided information on the magnitude [Hab(12.7 A) approximately 6.3 x 10(-3) cm-1] and decay [beta approximately 0.8 A-1, where kET alpha exp [-beta(d - do)]] of protein-mediated donor-acceptor electronic coupling. A reorganization energy lambda approximately 1.3 eV, due to coordination and solvation changes both at and between the ET sites, has been estimated using a rate expression that allows electron-vibration coupling to classical and quantum mechanical modes. The contribution to lambda from the porphyrin and peptide matrix is approximately 0.7 eV. Specific electron-tunneling pathways in the protein have been evaluated.
Electron Transport↗