Dulak J, Polus M, Guevara I, Polus A, Hartwich J, Dembińska-Kieć A
Department of Clinical Biochemistry, Jagiellonian University, Medical Faculty, Cracow, Poland.
J Physiol Pharmacol. 1997 Dec;48(4):689-97.
The generation of nitric oxide is regulated by several factors, including the substrates and cofactors supplementation. Decreased expression and activity of nitric oxide synthase as well as diminished amount of L-arginine or enzyme cofactors results in the inhibition of nitric oxide generation in vascular wall cells. GTP cyclohydrolase 1 is a key enzyme involved in the synthesis of tetrahydrobiopterin, one of the most important cofactors of NO synthases. We have demonstrated that oxidized LDL inhibit not only inducible nitric oxide synthase gene expression but also GTP cyclohydrolase I gene expression in interleukin-1 beta activated rat vascular smooth muscle cells in vitro. It is postulated that diminished availability of tetrahydrobiopterin may additionally impair the generation of nitric oxide in atherosclerosis.
一氧化氮的生成受多种因素调节，包括底物和辅助因子的补充。一氧化氮合酶的表达和活性降低以及L-精氨酸或酶辅助因子数量减少会导致血管壁细胞中一氧化氮生成受到抑制。鸟苷三磷酸环化水解酶1是参与四氢生物蝶呤合成的关键酶，四氢生物蝶呤是一氧化氮合酶最重要的辅助因子之一。我们已经证明，氧化型低密度脂蛋白在体外不仅抑制白细胞介素-1β激活的大鼠血管平滑肌细胞中诱导型一氧化氮合酶基因的表达，还抑制鸟苷三磷酸环化水解酶I基因的表达。据推测，四氢生物蝶呤可用性降低可能会进一步损害动脉粥样硬化中一氧化氮的生成。
