Summary: Glycoprotein (GP) Ibα ectodomain shedding has important implications for thrombosis and hemostasis. A disintegrin and metalloproteinase 17 (ADAM17) was identified to play an essen- tial role in agonist ...Summary: Glycoprotein (GP) Ibα ectodomain shedding has important implications for thrombosis and hemostasis. A disintegrin and metalloproteinase 17 (ADAM17) was identified to play an essen- tial role in agonist induced GPIbαshedding. The relationship of GPIbu shedding and ADAM 17 in the acute stage of atherosclerotic ischemic stroke (AIS) patients has not been thoroughly studied. A total of 306 patients and 230 controls matched for age, sex, race, history of hypertension and diabetes mel- litus were enrolled in the study. GPIbα, ADAM17, glycocalicin were detected by flow cytometry, Western blotting, and enzyme-linked immunosorbent assay (ELISA) respectively. Compared with the control group, the expression of GPIbα in patients with acute ischemic stroke was significantly lower (P=0.000, P〈0.01). Plasma glycocalicin and ADAM17 in AIS group were higher than those in con- trol group (P=0.699, P=0.000). Pearson's analysis showed glycocalicin bore no correlation with GPIbu in AIS patients (r=0.095, P〉0.05). GPIbα and National Institute of Health Stroke Scale (NIHSS) had negative correlation (r=-0.514, P〈0.01). Our findings indicate that ADAM 17 may be a risk factor for ischemic stroke in Chinese and the expression of GPIbα can serve as a measure for stroke severity.展开更多
Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic fac...Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic factorⅧ,integrin,and platelet glycoprotein lbα(GPlbα)to achieve multiple biological functions.During hemostasis,the A1 domain of VWF binds to GPIbαwhere platelets accumulate in the injured vascular endothelium.Due to forces generated by the hemodynamic gradient flow,the relations of bond-dissociation rates versus forces show that the lifetime of molecular bond has multiple states under the external force.We processed the experimental data of receptor-ligand in a single molecule obtained from optical tweezers by two different methods,including a Dudko-Hummer-Szabo equation,and another method combining force4ime history and force induced bond rupture.Then we used a recently developed physical equation regarding protein unfolding rate to fit our results.The lifetime of the bond between A1 and GPlbαobtained by the above mentioned two methods shows a'three-stage'change upon gradually increasing the external force.When the external force was below 8 pN,the lifetime of the bond deceased as the external force increased,which is a typical expression of a catch bond.The lifetime of the bond started to increase when the external force increased from 8 to 11 pN,and then decrease again when the external force increased to above 11 pN.Kim et al.used different processing methods and proposes a'flex-bond'model:the lifetime of the bond will decrease as the external force increases,then suddenly increase to a peak,and continue to decrease with the increase of force.A recently developed model based on the structural-elastic properties of molecules fits our data well,indicating that the bond formed by Al and GPlbαhas a catch-bond phenomenon in a certain interval of external forces,and a flex bond in other force intervals.In conclusion,A1-GPIbαbond will have a'slip-catch-slip'bond tendency.Our result provides a alternative understanding about the role of Al-GPlbαinteractions in the mechanism of hemostasis.展开更多
以V isua l C++6.0作为开发平台,基于GP IB总线结构,在W IN 2000系统下设计开发了GP IB仪器控制系统。给出了系统的硬件组成及软件设计方法,实现了HP 35670A和笔记本电脑通过GP IB接口板两者之间的通讯。为数据的进一步分析处理提供了...以V isua l C++6.0作为开发平台,基于GP IB总线结构,在W IN 2000系统下设计开发了GP IB仪器控制系统。给出了系统的硬件组成及软件设计方法,实现了HP 35670A和笔记本电脑通过GP IB接口板两者之间的通讯。为数据的进一步分析处理提供了一个良好的软件平台。展开更多
基金supported by the National Natural Science Foundation of China (No. 81072945)
摘要Summary: Glycoprotein (GP) Ibα ectodomain shedding has important implications for thrombosis and hemostasis. A disintegrin and metalloproteinase 17 (ADAM17) was identified to play an essen- tial role in agonist induced GPIbαshedding. The relationship of GPIbu shedding and ADAM 17 in the acute stage of atherosclerotic ischemic stroke (AIS) patients has not been thoroughly studied. A total of 306 patients and 230 controls matched for age, sex, race, history of hypertension and diabetes mel- litus were enrolled in the study. GPIbα, ADAM17, glycocalicin were detected by flow cytometry, Western blotting, and enzyme-linked immunosorbent assay (ELISA) respectively. Compared with the control group, the expression of GPIbα in patients with acute ischemic stroke was significantly lower (P=0.000, P〈0.01). Plasma glycocalicin and ADAM17 in AIS group were higher than those in con- trol group (P=0.699, P=0.000). Pearson's analysis showed glycocalicin bore no correlation with GPIbu in AIS patients (r=0.095, P〉0.05). GPIbα and National Institute of Health Stroke Scale (NIHSS) had negative correlation (r=-0.514, P〈0.01). Our findings indicate that ADAM 17 may be a risk factor for ischemic stroke in Chinese and the expression of GPIbα can serve as a measure for stroke severity.
基金supported by the National Science Foundation of China ( 11772133, 11372116)the Fundamental Research Funds for the Central Universities ( HUST 0118012051)
摘要Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic factorⅧ,integrin,and platelet glycoprotein lbα(GPlbα)to achieve multiple biological functions.During hemostasis,the A1 domain of VWF binds to GPIbαwhere platelets accumulate in the injured vascular endothelium.Due to forces generated by the hemodynamic gradient flow,the relations of bond-dissociation rates versus forces show that the lifetime of molecular bond has multiple states under the external force.We processed the experimental data of receptor-ligand in a single molecule obtained from optical tweezers by two different methods,including a Dudko-Hummer-Szabo equation,and another method combining force4ime history and force induced bond rupture.Then we used a recently developed physical equation regarding protein unfolding rate to fit our results.The lifetime of the bond between A1 and GPlbαobtained by the above mentioned two methods shows a'three-stage'change upon gradually increasing the external force.When the external force was below 8 pN,the lifetime of the bond deceased as the external force increased,which is a typical expression of a catch bond.The lifetime of the bond started to increase when the external force increased from 8 to 11 pN,and then decrease again when the external force increased to above 11 pN.Kim et al.used different processing methods and proposes a'flex-bond'model:the lifetime of the bond will decrease as the external force increases,then suddenly increase to a peak,and continue to decrease with the increase of force.A recently developed model based on the structural-elastic properties of molecules fits our data well,indicating that the bond formed by Al and GPlbαhas a catch-bond phenomenon in a certain interval of external forces,and a flex bond in other force intervals.In conclusion,A1-GPIbαbond will have a'slip-catch-slip'bond tendency.Our result provides a alternative understanding about the role of Al-GPlbαinteractions in the mechanism of hemostasis.