Tracking oxidation-induced alterations in fibrin clot formation by NMR-based methods.
Tracking oxidation-induced alterations in fibrin clot formation by NMR-based methods.
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DOI：
10.1038/s41598-021-94401-3
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发表时间：
2021-08-03
影响因子：
4.6
通讯作者：
Pervushin K
中科院分区：
文献类型：
--
作者：
Lau WH;White NJ;Yeo TW;Gruen RL;Pervushin K
血浆纤维蛋白原是一个重要的凝血因子，氧化后的翻译后修饰敏感。通过中断AαC domain structures. However, experimental evidence explaining how HOCl oxide impairs fibrinogen structure and function has not been demonstrated. We utilized polymerization studies and two dimensional-nuclear magnetic resonance spectrometry (2D-NMR) to investigate the hypothesis that HOCl oxide alters fibrinogen conference and T2 relaxation time of water protons in the fibrin gels. We have demonstrated that both HOCl oxide impairments of purified纤维蛋白原和在血浆纤维蛋白原溶液中添加纤维蛋白原溶液的横向聚集与纤维蛋白聚合的竞争抑制相似，使用重组AαC片段使用AαC419-502促进了纤维纤维效果。在纤维纤维状态下，Ibrinogen更紧凑，快速运动。 2D-NMR的分析反映出水质量是大量水（T2），并且在对照血浆中的中间水（T2I）增加了质量，并增加了氧化氧化物的T2较小的氧化液，并与HOCL氧化物的水平相关。水合壳中的水分分数为我们已经确认T2弛豫受到纤维的自组装和血浆纤维蛋白凝胶的刚度的影响。
Plasma fibrinogen is an important coagulation factor and susceptible to post-translational modification by oxidants. We have reported impairment of fibrin polymerization after exposure to hypochlorous acid (HOCl) and increased methionine oxidation of fibrinogen in severely injured trauma patients. Molecular dynamics suggests that methionine oxidation poses a mechanistic link between oxidative stress and coagulation through protofibril lateral aggregation by disruption of AαC domain structures. However, experimental evidence explaining how HOCl oxidation impairs fibrinogen structure and function has not been demonstrated. We utilized polymerization studies and two dimensional-nuclear magnetic resonance spectrometry (2D-NMR) to investigate the hypothesis that HOCl oxidation alters fibrinogen conformation and T2 relaxation time of water protons in the fibrin gels. We have demonstrated that both HOCl oxidation of purified fibrinogen and addition of HOCl-oxidized fibrinogen to plasma fibrinogen solution disrupted lateral aggregation of protofibrils similarly to competitive inhibition of fibrin polymerization using a recombinant AαC fragment (AαC 419–502). DOSY NMR measurement of fibrinogen protons demonstrated that the diffusion coefficient of fibrinogen increased by 17.4%, suggesting the oxidized fibrinogen was more compact and fast motion in the prefibrillar state. 2D-NMR analysis reflected that water protons existed as bulk water (T2) and intermediate water (T2i) in the control plasma fibrin. Bulk water T2 relaxation time was increased twofold and correlated positively with the level of HOCl oxidation. However, T2 relaxation of the oxidized plasma fibrin gels was dominated by intermediate water. Oxidation induced thinner fibers, in which less water is released into the bulk and water fraction in the hydration shell was increased. We have confirmed that T2 relaxation is affected by the self-assembly of fibers and stiffness of the plasma fibrin gel. We propose that water protons can serve as an NMR signature to probe oxidative rearrangement of the fibrin clot.
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DOI：
10.1016/j.jmr.2009.10.005
发表时间：
2010-01
期刊：
Journal of magnetic resonance (San Diego, Calif. : 1997)
影响因子：
--
作者：
Luo J;He X;d'Avignon DA;Ackerman JJ;Yablonskiy DA
通讯作者：
Yablonskiy DA
影响因子：
2.9
作者：
Gorkun, OV;Henschen-Edman, AH;Lord, ST
通讯作者：
Lord, ST
影响因子：
7.4
作者：
Martinez, Marissa;Weisel, John W.;Ischiropoulos, Harry
通讯作者：
Ischiropoulos, Harry
影响因子：
13.1
作者：
Cistola, David P.;Robinson, Michelle D.
通讯作者：
Robinson, Michelle D.
DOI：
10.1073/pnas.97.1.85
发表时间：
2000-01-04
影响因子：
11.1
作者：
Brown, JH;Volkmann, N;Cohen, C
通讯作者：
Cohen, C