Andrades M E, Lorenzi R, Berger M, Guimarães J A, Moreira J C F, Dal-Pizzol F
Centro de Estudos em Estresse Oxidativo, Dpto. Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. andrades
Chem Biol Interact. 2009 Aug 14;180(3):478-84. doi: 10.1016/j.cbi.2009.04.005. Epub 2009 May 3.
Glycolaldehyde (GA) is a highly reactive aldehyde that can be generated during inflammation and hyperglycemia. It can react with arginine and lysine residues impairing protein function. As inflammation and diabetes present haemostatic dysfunction, we hypothesized that GA could participate in this process. The aim of this study was to investigate if plasma incubated in the presence of GA presents alteration in the coagulation process. We also aimed to evaluate the role of fibrinogen in GA-induced haemostatic dysfunction. For this purpose, plasma and fibrinogen were each incubated separately, either in the presence or absence of 1 mM GA for 8 and 4 h, respectively. After that, plasma coagulation and fibrin polymerization kinetics were recorded, as well as the kinetic of plasma clot digestion and fibrinolysis protein carbonylation was quantified. An SDS-PAGE was run to check the presence of cross-linking between fibrinogen chains. GA induced a delay in plasma coagulation and in fibrin polymerization. Maximum absorbance decreased after GA treatment, indicating the generation of thinner fibers. Fibrin generated after complete coagulation showed resistance to enzymatic digestion, which could be related to the generation of thinner fibers. Protein carbonylation also increased after GA treatment. All parameters could be reversed with AMG (a carbonyl trap) co-treatment. The data presented herein indicate that GA causes post-translational modification of lysine and arginine residues, which are central to many events involving fibrinogen to fibrin conversion, as well as to fibrinolysis. These modifications lead to the generation of persistent clots and may contribute to mortality seen in pathologies such diabetes and sepsis.
乙醇醛（GA）是一种高反应性醛类物质，可在炎症和高血糖过程中产生。它能与精氨酸和赖氨酸残基发生反应，损害蛋白质功能。由于炎症和糖尿病会导致止血功能障碍，我们推测GA可能参与了这一过程。本研究的目的是探究在GA存在的情况下孵育的血浆在凝血过程中是否会出现变化。我们还旨在评估纤维蛋白原在GA诱导的止血功能障碍中的作用。为此，分别将血浆和纤维蛋白原在有或无1 mM GA的情况下孵育8小时和4小时。之后，记录血浆凝血和纤维蛋白聚合动力学，以及血浆凝块消化动力学，并对纤维蛋白溶解蛋白羰基化进行定量分析。进行SDS-PAGE检测纤维蛋白原链之间是否存在交联。GA导致血浆凝血和纤维蛋白聚合延迟。GA处理后最大吸光度降低，表明生成了更细的纤维。完全凝血后生成的纤维蛋白对酶消化具有抗性，这可能与生成更细的纤维有关。GA处理后蛋白质羰基化也增加。所有参数均可通过与AMG（一种羰基捕获剂）共同处理而逆转。本文提供的数据表明，GA会导致赖氨酸和精氨酸残基的翻译后修饰，这些修饰在许多涉及纤维蛋白原向纤维蛋白转化以及纤维蛋白溶解的事件中起着核心作用。这些修饰导致生成持久性凝块，并可能导致糖尿病和脓毒症等疾病中的死亡率升高。
