Strålin Pontus, Jacobsson Håkan, Marklund Stefan L
Department of Medical Biosciences, Clinical Chemistry, Umeå University Hospital, Byggnad 1A, S-901 85 Umeå, Sweden.
Biochim Biophys Acta. 2003 Jan 2;1619(1):1-8. doi: 10.1016/s0304-4165(02)00419-1.
Oxygen free radicals apparently play important roles in diseases of the blood vessel wall and increased secretion of superoxide radicals occurs in many situations. The vascular wall contains large amounts of extracellular superoxide dismutase (EC-SOD). The synthesis of the enzyme by the smooth muscle cells (SMC) is modulated by cytokines, growth factors, and vasoactive factors. Here we studied the effects of oxidants (pyrogallol, xanthine oxidase, Cu and Fe), antioxidants (SOD, catalase, and ascorbate), glutathione modulation (n-acetylcysteine and buthionine sulfoximine) and nitric oxide on EC-SOD expression by human vascular SMCs. Generally, the responses in EC-SOD synthesis were small, and no changes were noted in mRNA levels. High concentrations of some of the agents caused reductions in EC-SOD synthesis, mostly concomitantly with toxic effects on the cells. Cell cultures are normally ascorbate deficient, and addition of ascorbate to approach physiological levels doubled the EC-SOD content. Iron ions up-regulated EC-SOD synthesis but also blocked the secretion of the enzyme. Only down-regulation was found by NO*-releasing compounds.In conclusion, there is limited response to oxidant stress of EC-SOD synthesis by SMCs on a cell-autonomous level. The synthesis appears mainly regulated by factors coordinating concerted tissue responses.
氧自由基显然在血管壁疾病中起重要作用，并且在许多情况下超氧阴离子自由基的分泌会增加。血管壁含有大量细胞外超氧化物歧化酶（EC-SOD）。平滑肌细胞（SMC）合成该酶受到细胞因子、生长因子和血管活性因子的调节。在此，我们研究了氧化剂（邻苯三酚、黄嘌呤氧化酶、铜和铁）、抗氧化剂（超氧化物歧化酶、过氧化氢酶和抗坏血酸）、谷胱甘肽调节（N-乙酰半胱氨酸和丁硫氨酸亚砜胺）以及一氧化氮对人血管SMC中EC-SOD表达的影响。一般来说，EC-SOD合成的反应较小，且mRNA水平未观察到变化。某些试剂的高浓度导致EC-SOD合成减少，大多同时伴有对细胞的毒性作用。细胞培养通常缺乏抗坏血酸，添加抗坏血酸使其接近生理水平可使EC-SOD含量增加一倍。铁离子上调EC-SOD合成，但也阻断该酶的分泌。仅发现释放NO*的化合物可下调EC-SOD合成。总之，在细胞自主水平上，SMC对EC-SOD合成的氧化应激反应有限。其合成似乎主要受协调一致的组织反应的因子调节。
