Rho associated coiled-coil kinase-1 regulates collagen-induced phosphatidylserine exposure in platelets.
Rho associated coiled-coil kinase-1 regulates collagen-induced phosphatidylserine exposure in platelets.
复制标题
DOI：
10.1371/journal.pone.0084649
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Thiagarajan P
中科院分区：
文献类型：
--
作者：
Dasgupta SK;Le A;Haudek SB;Entman ML;Rumbaut RE;Thiagarajan P
磷脂酰丝氨酸的跨双层运动介导了胶原刺激过程中血小板的促凝活性。Rho相关卷曲螺旋激酶（ROCK）抑制剂Y-27632抑制衰老诱导的磷脂酰丝氨酸暴露，但不抑制活化诱导的磷脂酰丝氨酸暴露。为了进一步研究具体的机制，我们现在利用ROCK 1亚型基因缺失的小鼠。 与野生型血小板相比，ROCK 1缺陷小鼠血小板暴露出更多的磷脂酰丝氨酸，并在胶原蛋白活化后产生更多的凝血酶。与野生型血小板相比，血小板形状变化、聚集或钙反应没有显著缺陷。胶原刺激的ROCK 1缺陷型血小板也显示Lim激酶-1和cofilin-1的磷酸化水平降低。然而，肌球蛋白磷酸酶亚基-1（MYPT 1）或肌球蛋白轻链（MLC）的磷酸化水平没有降低。在体内光/染料诱导的内皮损伤/血栓形成模型中，与野生型同窝小鼠相比，ROCK 1缺陷小鼠的提睾肌小静脉闭塞时间较短（3.16 ± 1.33 min vs 6.6 ± 2.6 min; p = 0.01）。 这些研究将ROCK 1定义为血小板中胶原诱导的磷脂酰丝氨酸暴露的新调节剂，其对血栓形成具有功能性后果。这种作用是钙信号的下游，并通过Lim激酶-1/ cofilin-1诱导的细胞骨架变化介导。
The transbilayer movement of phosphatidylserine mediates the platelet procoagulant activity during collagen stimulation. The Rho-associated coiled-coil kinase (ROCK) inhibitor Y-27632 inhibits senescence induced but not activation induced phosphatidylserine exposure. To investigate further the specific mechanisms, we now utilized mice with genetic deletion of the ROCK1 isoform. ROCK1-deficient mouse platelets expose significantly more phosphatidylserine and generate more thrombin upon activation with collagen compared to wild-type platelets. There were no significant defects in platelet shape change, aggregation, or calcium response compared to wild-type platelets. Collagen-stimulated ROCK1-deficient platelets also displayed decreased phosphorylation levels of Lim Kinase-1 and cofilin-1. However, there was no reduction in phosphorylation levels of myosin phosphatase subunit-1 (MYPT1) or myosin light chain (MLC). In an in vivo light/dye-induced endothelial injury/thrombosis model, ROCK1-deficient mice presented a shorter occlusion time in cremasteric venules when compared to wild-type littermates (3.16 ± 1.33 min versus 6.6 ± 2.6 min; p = 0.01). These studies define ROCK1 as a new regulator for collagen-induced phosphatidylserine exposure in platelets with functional consequences on thrombosis. This effect was downstream of calcium signaling and was mediated by Lim Kinase-1 / cofilin-1-induced cytoskeletal changes.
登录
查看更多内容
DOI：
10.3324/haematol.2009.006585
发表时间：
2009-10-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Jeremy, Kris P.;Plummer, Zoe E.;Avent, Neil D.
通讯作者：
Avent, Neil D.
影响因子：
64.5
作者：
Mason, Kylie D.;Carpinelli, Marina R.;Kile, Benjamin T.
通讯作者：
Kile, Benjamin T.
影响因子：
20.3
作者：
Bergmeier, Wolfgang;Oh-hora, Masatsugu;Feske, Stefan
通讯作者：
Feske, Stefan
影响因子：
7.8
作者：
Dasgupta, Swapan K.;Guchhait, Prasenjit;Thiagarajan, Perlimal
通讯作者：
Thiagarajan, Perlimal
影响因子：
4.8
作者：
Paul, BZS;Daniel, JL;Kunapuli, SP
通讯作者：
Kunapuli, SP