Egorina Elena M, Sovershaev Mikhail A, Kondratiev Timofei V, Olsen Jan O, Tveita Torkjel, Østerud Bjarne
Department of Biochemistry, Institute of Medical Biology, University of Tromsø, N-9037, Tromsø, Norway.
Arterioscler Thromb Vasc Biol. 2006 Oct;26(10):2401-6. doi: 10.1161/01.ATV.0000240519.46754.9c. Epub 2006 Aug 10.
Triggering of tissue factor (TF)-mediated blood coagulation leads to the development of disseminated intravascular coagulation during rewarming from hypothermia. We studied post-rewarming TF levels, activity, and surface redistribution, along with the regulation of TF gene transcription in mononuclear cells (MNCs) obtained from an in vivo rat model.
Rewarming after a 5-hour episode of 15 degrees C hypothermia caused an increase in TF activity, protein levels, and externalization of TF antigen in rat MNCs. This was accompanied by a dramatic elevation of c-Jun and JNK phosphorylation, and the absence of EGR-1 and NF-kappaB activation. To search for a stimulus to counteract c-Jun-mediated induction of TF activity in MNCs from rewarmed rats, we applied heat shock pretreatment one day before the hypothermia/rewarming experiment. This restored post-rewarming TF activity, protein levels, and surface-to-total TF ratio in rat MNCs to normothermic levels. Furthermore, in heat shock-pretreated animals, rewarming failed to increase phosphorylated c-Jun and JNK levels. We attribute this to the profound overexpression of heat shock protein 70 and inhibition of JNK.
MNCs respond to rewarming from hypothermia by an induction of active TF antigen. This effect is dependent on c-Jun activation and is abolished by heat shock pretreatment.
在从低温复温过程中，组织因子（TF）介导的血液凝固触发会导致弥散性血管内凝血的发生。我们研究了复温后TF水平、活性和表面再分布情况，以及从体内大鼠模型获得的单核细胞（MNCs）中TF基因转录的调控。
在15℃低温5小时后复温，导致大鼠MNCs中TF活性、蛋白水平升高，TF抗原外化。这伴随着c-Jun和JNK磷酸化的显著升高，以及早期生长反应蛋白-1（EGR-1）和核因子κB（NF-κB）激活的缺失。为了寻找一种刺激来抵消复温大鼠MNCs中c-Jun介导的TF活性诱导，我们在低温/复温实验前一天进行热休克预处理。这将复温后大鼠MNCs中的TF活性、蛋白水平以及表面TF与总TF的比例恢复到正常体温水平。此外，在热休克预处理的动物中，复温未能增加磷酸化c-Jun和JNK水平。我们将此归因于热休克蛋白70的大量过表达和JNK的抑制。
MNCs对低温复温的反应是诱导活性TF抗原。这种效应依赖于c-Jun激活，并且通过热休克预处理被消除。
