Martínez-Martínez I, Ordóñez A, Guerrero J A, Pedersen S, Miñano A, Teruel R, Velázquez L, Kristensen S R, Vicente V, Corral J
Centro Regional de Hemodonación, Universidad de Murcia, Ronda de Garay S/N, Murcia 30003, Spain.
FEBS Lett. 2009 Oct 6;583(19):3165-70. doi: 10.1016/j.febslet.2009.07.062. Epub 2009 Sep 1.
We studied the effect of acrolein, an alpha,beta-unsaturated aldehyde that causes adduct-modification of lysine, cysteine, and histidine residues, on antithrombin, a key anticoagulant serpin. Intrinsic fluorescence, functionality (anti-FXa and anti-IIa activity), heparin affinity and conformational features of plasma and purified antithrombin were evaluated. In vivo experiments were carried out in mice. Intrinsic fluorescence showed a two-step conformational change. Acrolein, even at low dose, impaired the anticoagulant function of purified antithrombin by affecting its heparin affinity. However, higher concentrations of acrolein and long incubations are required to cause mild functional effects on plasma antithrombin and mice.
我们研究了丙烯醛（一种能导致赖氨酸、半胱氨酸和组氨酸残基发生加合物修饰的α,β-不饱和醛）对关键抗凝丝氨酸蛋白酶抑制剂抗凝血酶的影响。评估了血浆和纯化抗凝血酶的内在荧光、功能（抗FXa和抗IIa活性）、肝素亲和力和构象特征。在小鼠体内进行了实验。内在荧光显示出两步构象变化。即使是低剂量的丙烯醛，也会通过影响其肝素亲和力而损害纯化抗凝血酶的抗凝功能。然而，需要更高浓度的丙烯醛和更长的孵育时间才会对血浆抗凝血酶和小鼠产生轻微的功能影响。
