戴克胜
主要从事血栓与止血、细胞信号转导及凋亡调控机制和空间生理学研究
个性化签名
- 姓名:戴克胜
- 目前身份:
- 担任导师情况:
- 学位:
-
学术头衔:
博士生导师, 教育部“新世纪优秀人才支持计划”入选者
- 职称:-
-
学科领域:
生理学
- 研究兴趣:主要从事血栓与止血、细胞信号转导及凋亡调控机制和空间生理学研究
戴克胜,北京航空航天大学“蓝天学者”特聘教授,生物与医学工程学院教授、博士生导师。毕业于苏州大学,获医学博士学位,美国伊利诺伊大学(University of Illinois)博士后。主要从事血栓与止血、细胞信号转导及凋亡调控机制和空间生理学研究。近年来在Blood、Circulation Research等国内、外期刊发表学术著作80余篇,受理的中、外发明专利3项。曾获全国优秀博士学位论文,美国博士后研究人员奖(Postdoctoral Fellowship Award)等奖励、资助,入选教育部“新世纪优秀人才支持计划”。为中国病理生理学会微循环专业委员会委员,中国中西医结合学会微循环专业委员会委员。Frontiers of Biology in China等杂志编委。
-
主页访问
2606
-
关注数
0
-
成果阅读
532
-
成果数
12
戴克胜, Kesheng Dai, Richard Bodnar, Michael C. Berndt, and Xiaoping Du
Blood. 2005; 106: 1975-1981,-0001,():
-1年11月30日
The platelet receptor for von Willebrand factor (VWF), glycoprotein (GP) Ib–IX, mediates platelet adhesion and activation. The cytoplasmic domains of the GPIb α and β subunits contain binding sites for the phosphorylation-dependent signaling molecule, 14-3-3. Here we show that a novel membrane-permeable inhibitor of 14-3-3-GPIbα interaction, MPα C, potently inhibited VWF binding to platelets and VWF-mediated platelet adhesion under flow conditions. MPαC also inhibited VWF-dependent platelet agglutination induced by ristocetin. Furthermore, activation of the VWF binding function of GPIb-IX induced by GPIbβ dephosphorylation is diminished by mutagenic disruption of the 14-3-3 binding site in the C-terminal domain of GPIbα, mimicking MPα C-induced inhibition, indicating that the inhibitory effect of MPαC is likely to be caused by disruption of 14-3-3 binding to GPIbα. These data suggest a novel 14-3-3-dependent regulatory mechanism that controls the VWF binding function of GPIb-IX, and also suggest a new type of antiplatelet agent that may be potentially useful in preventing or treating thrombosis.
-
36浏览
-
0点赞
-
0收藏
-
0分享
-
239下载
-
0评论
-
引用
【期刊论文】Calmodulin antagonists induce platelet apoptosis
戴克胜, Zhicheng Wang, Suping Li, Quanwei Shi, Rong Yan, Guanglei Liu, Kesheng Dai*
Thrombosis Research 125 (2010) 340-350,-0001,():
-1年11月30日
Calmodulin (CaM) antagonists induce apoptosis in various tumor models and inhibit tumor cell invasion and metastasis, thus some ofwhich have been extensively used as anti-cancer agents. In platelets, CaMhas been found to bind directly to the cytoplasmic domains of several platelet receptors. Incubation of platelets with CaM antagonists impairs the receptors-related platelet functions. However, it is still unknown whether CaM antagonists induce platelet apoptosis. Here we show that CaM antagonists N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7), tamoxifen (TMX), and trifluoperazine (TFP) induce apoptotic events in human platelets, including depolarization of mitochondrial inner transmembrane potential, caspase-3 activation, and phosphatidylserine exposure. CaMantagonists did not incur platelet activation as detected by P-selectin surface expression and PAC-1 binding. However, ADP-, botrocetin-, and α-thrombin-induced platelet aggregation, platelet adhesion and spreading on von Willebrand factor surface were significantly reduced in platelets pretreatedwith CaM antagonists. Furthermore, cytosolic Ca2+ levelswere obviously elevated by both W7and TMX, and membrane-permeable Ca2+ chelator BAPTA AMsignificantly reduced apoptotic events in platelets induced by W7. Therefore, these findings indicate that CaM antagonists induce platelet apoptosis. The elevation of the cytosolic Ca2+ levels may be involved in the regulation of CaM antagonists-induced platelet apoptosis.
Platelets, Calmodulin antagonists, Apoptosis, Tamoxifen, Thrombocytopenia
-
70浏览
-
0点赞
-
0收藏
-
0分享
-
100下载
-
0评论
-
引用
【期刊论文】Effects of microgravity and hypergravity on platelet functions
戴克胜, Kesheng Dai, Yuedan Wang, Rong Yan, Quanwei Shi, Zhicheng Wang, Yanhong Yuan, , Hong Cheng, Suping Li, Yubo Fan, Fengyuan Zhuang
Thromb Haemost 2009; 101: 902-910,-0001,():
-1年11月30日
Many serious thrombotic and haemorrhagic diseases or fatalities have been documented in human being exposed to microgravity or hypergravity environments, such as crewmen in space, roller coaster riders, and aircrew subjected to high-G training. Some possible related organs have been examined to explore the mechanisms underlying these gravity change-related diseases. However, the role of platelets which are the primary players in both thrombosis and haemostasis is unknown. Here we show that platelet aggregation induced by ristocetin or collagen and platelet adhesion to von Willebrand factor (VWF) were significantly decreased after platelets were exposed to simulated microgravity. Conversely, these platelet functions were increased after platelets were exposed to hypergravity. The tail bleeding time in vivo was significantly shortened in mice exposed to high-G force, whereas, was prolonged in hindlimb un-loaded mice. Furthermore, three of 23 mice died after 15 minutes of -8Gx stress. Platelet thrombi disseminated in the heart ventricle and blood vessels in the brain, lung, and heart from the dead mice. Finally, glycoprotein (GP) Ibα surface expression and its association with the cytoskeleton were significantly decreased in platelets exposed to simulated microgravity, and obviously increased in hypergravity-exposed platelets. These data indicate that the platelet functions are inhibited in microgravity environments, and activated under high-G conditions, suggesting a novel mechanism for gravity change-related haemorrhagic and thrombotic diseases. This mechanism has important implications for preventing and treating gravity change-related diseases, and also suggests that special attentions should be paid to human actions under different gravity conditions.
Platelets, thrombosis, haemorrhage, simulated microgravity, hypergravity
-
38浏览
-
0点赞
-
0收藏
-
0分享
-
179下载
-
0评论
-
引用
【期刊论文】Hypergravity results in human platelet hyperactivity
戴克胜, S. Li, Q. Shi, Z. Wang, R. Yan, H. Cheng and K. Dai
J Physiol Biochem, 65 (2), 147-156, 2009,-0001,():
-1年11月30日
Thrombotic diseases or fatalities have been reported to occasionally occur under conditions of hypergravity although the mechanism is still unclear. To investigate the effect of hypergravity on platelets that are the primary players in thrombus formation, platelet rich plasma (PRP) or washed platelets were exposed to hypergravity at 8 G for 15 minutes. No platelet aggregation was induced by 8 G alone, whereas ristocetin or collagen-induced platelet aggregation was significantly increased. The number of platelets adherent to immobilized fibrinogen and the area of platelets spreading on von Willbrand factor (VWF) matrix were increased simultaneously. Flow cytometry assay indicated that integrin αIIbβ3 was partially activated in 8 Gexposed platelets, but there was no significant difference in P-selectin surface expression between platelets treated with 8G and 1G control. The results indicate that hypergravity leads to human platelet hyperactivity, but fails to incur essential platelet activation events, suggesting a novel mechanism for thrombotic diseases occurring under hypergravitional conditions.
Platelet, Integrin αIIbβ3, Hypergravity, P-selectin, Hyperactivity, Thrombosis
-
34浏览
-
0点赞
-
0收藏
-
0分享
-
93下载
-
0评论
-
引用
【期刊论文】Hyperthermia induces platelet apoptosis and glycoprotein Iba ectodomain shedding
戴克胜, ZHICHENG WANG*, QUANWEI SHI*, SUPING LI, JUAN DU, JUN LIU, & KESHENG DAI
Platelets, Month?? 2010; ??(?): 1-9,-0001,():
-1年11月30日
Hemorrhage is a significant pathological feature of some fever or hyperthermia-related diseases, such as dengue fever and heatstroke. Although the mechanisms of hemorrhage in these diseases are thought to be complex, whether there is an association between hemorrhage and hyperthermia or fever remains unclear. Platelets play a central role in maintaining integrity of endothelium and biological hemostasis. To explore the effect of hyperthermia on platelet physiology, platelet-rich plasma or washed platelets were incubated at hypothermia (22℃), normothermia (37℃) or hyperthermia (40 and 42℃) for 1 or 2 hours. ADP and α-thrombin induced platelet aggregations were obviously reduced in platelets incubated at hyperthermia. Hyperthermia induced apoptotic events in platelets, including depolarization of mitochondrial inner transmembrane potential, caspase-3 dependent gelsolin cleavage and phosphatidylserine exposure. Furthermore, hyperthermia incurred platelet glycoprotein Ibβ ectodomain shedding. Thus, these data suggest that hyperthermia induces platelet apoptosis and dysfunction. These findings have important implications for the pathogenesis of hemorrhage in fever or hyperthermia-related diseases, and also suggest that attention should be paid to platelet apoptosis under relatively high temperature conditions.
Platelets, apoptosis, hemorrhage, hyperthermia, fever, GPIb shedding
-
72浏览
-
0点赞
-
0收藏
-
0分享
-
91下载
-
0评论
-
引用
戴克胜, Yanhong Yuan, * Weilin Zhang, * Rong Yan, Yi Liao, Lili Zhao, Changgeng Ruan, Xiaoping Du, Kesheng Dai
Circ Res. 2009; 105: 1177-1185,-0001,():
-1年11月30日
Rationale: The interaction between platelet glycoprotein (GP) Ib-IX and von Willebrand factor (VWF) is initiated by conformational changes in immobilized VWF and is also regulated by the intraplatelet proteins 14-3-3ζand filamin A. Both 14-3-3ζand filamin A associate with the cytoplasmic domain of GPIb, whereas little is known about their relationship in regulating the VWF binding function of GPIb-IX. Objective: To explore the mechanism underlying the roles of 14-3-3ζand filamin A in regulating the VWF binding function of GPIb-IX. Methods and Results: A truncation mutant of GPIbζ(△565) deleting the C-terminal 14-3-3ζbinding sites retained 14-3-3ζbinding function, in contrast, deletion of the C-terminal residues 551 to 610 of GPIb totally abolished 14-3-3ζbinding, indicating that the residues 551 to 564 of GPIbζare important in the interaction between 14-3-3ζ and GPIb-IX. An antibody recognizing phosphorylated R557GpSLP561 sequence reacted with GPIbζsuggesting phosphorylation of a population of GPIbζmolecules at Ser559, and a membrane permeable phosphopeptide (MP-P), R557GpSLP561 corresponding to residues 557 to 561 of GPIb eliminated the association of 14-3-3ζwith △565. MP-P also promoted GPIb-IX association with the membrane skeleton, and inhibited ristocetin-induced platelet agglutination, VWF binding to platelets and platelet adhesion to immobilized VWF. Furthermore, a GPIb-IX mutant replacing Ser559 of GPIbζ with alanine showed an enhanced association with the membrane skeleton, reduced ristocetin-induced VWF binding, and diminished ability to mediate cell adhesion to VWF under flow conditions. Conclusions: These data suggest a phosphorylation-dependent binding of 14-3-3ζto central filamin A binding site of GPIbζ, and the dimeric 14-3-3ζ binding to both the C-terminal site and central RGpSLP site inhibits GPIb-IX association with the membrane skeleton and promotes the VWF binding function of GPIb-IX.
platelets, GPIb, 14-3-3ζ, von Willebrand factor, thrombosis
-
24浏览
-
0点赞
-
0收藏
-
0分享
-
61下载
-
0评论
-
引用
戴克胜, Suping Li, , * Quanwei Shi, * Guanglei Liu, Weilin Zhang, Zhicheng Wang, Yuedan Wang, and Kesheng Dai
J Appl Physiol 108: 000-000, 2010,-0001,():
-1年11月30日
Serious thrombotic and hemorrhagic problems or even fatalities evoked by either microgravity or hypergravity occur commonly in the world. We recently reported that platelet functions are inhibited in microgravity environments and activated under high-G conditions, which reveals the pathogenesis for gravity change-related hemorrhagic and thrombotic diseases. However, the mechanisms of platelet functional variations under different gravity conditions remain unclear. In this study we show that the amount of filamin A coimmunoprecipitated with GPIbα was enhanced in platelets exposed to modeled microgravity and, in contrast, was reduced in 8G-exposed platelets. Hypergravity induced actin filament formation and redistribution, whereas actin filaments were reduced in platelets treated with modeled microgravity. Furthermore, intracellular Ca2+ levels were elevated by hypergravity. Pretreatment of platelets with the cell-permeable Ca2+ chelator BAPTA-AM had no effect on cytoskeleton reorganization induced by hypergravity but significantly reduced platelet aggregation induced by ristocetin/hypergravity. Two anti-platelet agents, aspirin and tirofiban, effectively reversed the shortened tail bleeding time and reduced the death rate of mice exposed to hypergravity. Furthermore, the increased P-selectin surface expression was obviously reduced in platelets from mice treated with aspirin/hypergravity compared with those from mice treated with hypergravity alone. These data suggest that the actin cytoskeleton reorganization and intracellular Ca2+ level play key roles in the regulation of platelet functions in different gravitational environments. The results with anti-platelet agents not only further confirm the activation of platelets in vivo but also suggest a therapeutic potential for hypergravity-induced thrombotic diseases.
platelets, cytoskeleton, calcium, modeled microgravity, hypergravity
-
33浏览
-
0点赞
-
0收藏
-
0分享
-
85下载
-
0评论
-
引用
戴克胜, Kesheng Dai a, *, , Rong Yan a, Suping Li a, Yubo Fan a, Fengyuan Zhuang a, Changgeng Ruan b
Thrombosis Research 124 (2009) 101-109,-0001,():
-1年11月30日
Introduction: The interaction of platelet glycoprotein (GP) Ibα with von Willebrand factor (VWF) exposed at the injured vessel wall initiates platelet adhesion and thrombus formation. Thus GPIbα ectodomain shedding has important implications for thrombosis and hemostasis. A disintegrin and metalloproteinase 17 (ADAM17) was identified recently to play an essential role in agonist induced GPIbα shedding. Here we show that prolonged inhibition of protein kinase A (PKA) results in metalloproteinase-dependent GPIbα shedding. Methods and Results: GPIbα was shed from platelets prolongedly incubated with PKA inhibitors in a dosedependent manner. In platelets treated with PKA inhibitor H89, the level of GPIbα shedding was significantly higher than that in calcium ionophore or α-thrombin treated platelets, however, P-selectin surface expression was significantly lower. PKA inhibition mediated GPIbα shedding was reversed by PKA activator forskolin and partially inhibited by membrane-permeable calpain inhibitors. Furthermore, the metalloproteinase inhibitor GM6001 or EDTA completely inhibited H89 induced GPIbα shedding, indicating that itwasmetalloproteinasedependent. Time course experiments revealed that the maximum GPIbαshedding occurred at 30 minutes after treatment with PKA inhibitor. Platelets prolongedly treated with PKA inhibitor exhibited significant decrease in botrocetin-induced aggregation and shear-induced adhesion on VWF. Conclusions: These data show that prolonged inhibition of PKA results inmetalloproteinase-dependent platelet GPIbα ectodomain shedding. This finding has physiological implications for hemostasis and limiting thrombus infinite formation after platelet activation, and it also suggests a novel strategy to develop new drugs for thrombotic diseases.
Glycoprotein Ibα, Protein kinase A, Shedding, Metalloproteinase, Thrombosis, Platelet
-
43浏览
-
0点赞
-
0收藏
-
0分享
-
53下载
-
0评论
-
引用
【期刊论文】Role of cAMP-dependent protein kinase in the regulation of platelet procoagulant activity
戴克胜, Rong Yan, Zhicheng Wang, Yanhong Yuan, Hong Cheng, Kesheng Dai*
Archives of Biochemistry and Biophysics 485 (2009) 41-48,-0001,():
-1年11月30日
The membrane microparticle (MP) formation and phosphatidylserine (PS) exposure evoked by platelet activation provide catalytic surfaces for thrombin generation. Several reports have indicated the effects of cAMP-elevating agents on agonist-induced MP formation and PS exposure; however, the mechanism still remains unclear. Here we show that inhibition of basal cyclic AMP-dependent protein kinase (PKA) activity incurred platelet MP formation and PS exposure. Pretreatment of platelets with cAMP-elevating agent, forskolin, abolished thrombin plus collagen-induced MP formation and PS exposure, and obviously decreased calcium ionophore-evoked MP shedding. Moreover, the inhibitory effects of forskolin on agonists-induced MP formation and PS exposure were reversed by the PKA inhibitor H89. PKA inhibitor-induced MP formation was dose-dependently inhibited by calpain inhibitor MDL28170, and forskolin abrogated thrombin plus collagen-induced calpain activation. In conclusion, PKA plays key roles in the regulation of platelet MP formation and PS exposure. PKA-mediated MP shedding is dependent on calpain activation.
Platelet, Microparticle, Phosphatidylserine, cAMP-dependent protein kinase (, PKA), , Calpain
-
63浏览
-
0点赞
-
0收藏
-
0分享
-
55下载
-
0评论
-
引用
戴克胜, Hong Cheng, Rong Yan, Suping Li, Yanhong Yuan, Jun Liu, Changgeng Ruan, and Kesheng Dai
Am J Physiol Heart Circ Physiol 297: H2128-H2135, 2009.,-0001,():
-1年11月30日
Shear-induced platelet adhesion through the interaction of glycoprotein (GP) Ibα with von Willebrand factor (VWF) exposed at the injured vessel wall or atherosclerotic plaque rupture is a prerequisite for the physiological hemostatic process or pathological thrombus formation in stenosed arteries. Here we show that shear-induced interaction of platelets with immobilized VWF results in GPIbα ectodomain shedding. Washed platelets were exposed to VWF-coated glass capillary or cone-and-plate viscometer at different shear rates, and GPIbα ectodomain was shed from platelets, while a small mass of GPIbα COOH-terminal peptide, ~17 kDa, was increased correspondingly. The extent of GPIbα shedding was enhanced with the concentration of immobilized VWF and the time duration of constant shear stress, whereas it was obviously reduced with the decreased number of adherent platelets. Pretreatment of platelets with membrane-permeable calpain inhibitors and metalloproteinase inhibitor abolished shearinduced GPIbα shedding. Furthermore, GPIbα shedding was obviously diminished by anti-integrin-αIIbβ3 monoclonal antibody SZ21, phosphatidylinositol 3-kinase inhibitor wortmannin, and cell-permeable calcium chelator 1, 2-bis(o-aminophenoxy)ethane-N, N, N′, N′-tetraacetic acid. These results indicate that shear-induced platelet-VWF interaction results in calpain and metalloproteinase-dependent GPIb ectodomain shedding. These findings not only have a physiological implication in understanding the presence of glycocalicin in normal circulation, but also suggest a novel mechanism for the negative regulation of platelet function and the limitation of platelet thrombus infinite formation under pathophysiological flow conditions.
thrombosis, intergrin-αIIbβ3, metalloproteinase
-
28浏览
-
0点赞
-
0收藏
-
0分享
-
67下载
-
0评论
-
引用