State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Protein Cell. 2012 Aug;3(8):627-40. doi: 10.1007/s13238-012-2057-y. Epub 2012 Jul 26.
Fibrinogen is a key protein involved in coagulation and its deposition on blood vessel walls plays an important role in the pathology of atherosclerosis. Although the causes of fibrinogen (fibrin) deposition have been studied in depth, little is known about the relationship between fibrinogen deposition and reactive carbonyl compounds (RCCs), compounds which are produced and released into the blood and react with plasma protein especially under conditions of oxidative stress and inflammation. Here, we investigated the effect of glycolaldehyde on the activity and deposition of fibrinogen compared with the common RCCs acrolein, methylglyoxal, glyoxal and malondialdehyde. At the same concentration (1 mmol/L), glycolaldehyde and acrolein had a stronger suppressive effect on fibrinogen activation than the other three RCCs. Fibrinogen aggregated when it was respectively incubated with glycolaldehyde and the other RCCs, as demonstrated by SDS-PAGE, electron microscopy and intrinsic fluorescence intensity measurements. Staining with Congo Red showed that glycolaldehyde- and acrolein-fibrinogen distinctly formed amyloid-like aggregations. Furthermore, the five RCCs, particularly glycolaldehyde and acrolein, delayed human plasma coagulation. Only glycolaldehyde showed a markedly suppressive effect on fibrinogenesis, none did the other four RCCs when their physiological blood concentrations were employyed, respectively. Taken together, it is glycolaldehyde that suppresses fibrinogenesis and induces protein aggregation most effectively, suggesting a putative pathological process for fibrinogen (fibrin) deposition in the blood.
纤维蛋白原是参与凝血的关键蛋白，其在血管壁上的沉积在动脉粥样硬化的病理学中起着重要作用。尽管纤维蛋白原（纤维蛋白）沉积的原因已经被深入研究，但对于纤维蛋白原沉积与反应性羰基化合物（RCCs）之间的关系知之甚少，这些化合物是在氧化应激和炎症等条件下产生并释放到血液中，并与血浆蛋白反应的化合物。在这里，我们研究了与常见的 RCCs 丙烯醛、甲基乙二醛、乙二醛和丙二醛相比，乙二醇醛对纤维蛋白原活性和沉积的影响。在相同浓度（1mmol/L）下，乙二醇醛和丙烯醛对纤维蛋白原激活的抑制作用强于其他三种 RCCs。当分别用乙二醇醛和其他 RCCs 孵育时，纤维蛋白原聚集，如 SDS-PAGE、电子显微镜和本征荧光强度测量所示。刚果红染色表明，乙二醇醛-和丙烯醛-纤维蛋白原明显形成类淀粉样聚集。此外，五种 RCCs，特别是乙二醇醛和丙烯醛，延迟了人血浆凝固。只有乙二醇醛对纤维生成有明显的抑制作用，而当使用其生理血液浓度时，其他四种 RCCs 均没有。总之，是乙二醇醛最有效地抑制纤维生成并诱导蛋白聚集，这表明血液中纤维蛋白原（纤维蛋白）沉积的潜在病理过程。
