Blood vessels either form de novo through the process of vasculogenesis or through angiogenesis that involves the sprouting and proliferation of endothelial cells in pre-existing blood vessels. A complex interactive n...Blood vessels either form de novo through the process of vasculogenesis or through angiogenesis that involves the sprouting and proliferation of endothelial cells in pre-existing blood vessels. A complex interactive network of signaling cascades downstream from at least three of the nine known G-protein-coupled sphingosine-1-phosphate (S1P) receptors act as a prime effector of neovascularization that occurs in embryonic development and in association with various pathologies. This review focuses on the current knowledge of the roles of S1P signaling in vasculogenesis and angiogenesis, with particular emphasis on vascular cell adhesion and motility responses.展开更多
BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric ...BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those of the controls, and this phenomenon wa展开更多
β-arrestin是一类重要的信号调控蛋白和支架蛋白（scaffold）。在G蛋白偶联受体（G-protein-OOU-piedreceptor，GPCR）信号转导中，β-arrestin不但可以作为GPCR信号的负性调控分子，还能作为支架蛋白促进GPCR对其他信号通路的激活，...β-arrestin是一类重要的信号调控蛋白和支架蛋白（scaffold）。在G蛋白偶联受体（G-protein-OOU-piedreceptor，GPCR）信号转导中，β-arrestin不但可以作为GPCR信号的负性调控分子，还能作为支架蛋白促进GPCR对其他信号通路的激活，如有丝分裂原激活蛋白激酶（mitogen-activated protein kinase，MAPK）途径。另外β-arrestin还能与转录因子调节蛋白，如IKB和Mdm2相互作用问接调节NF-κB和P53介导的转录。展开更多
目的探讨Apelin受体与G蛋白之间的相互作用。方法在HEK293T细胞中建立Apelin受体与各亚型G蛋白的过表达体系,利用荧光共振能量转移技术(fluorescence resonance energy transfer technology,FRET)实时、动态、连续的监测Apelin受体与G...目的探讨Apelin受体与G蛋白之间的相互作用。方法在HEK293T细胞中建立Apelin受体与各亚型G蛋白的过表达体系,利用荧光共振能量转移技术(fluorescence resonance energy transfer technology,FRET)实时、动态、连续的监测Apelin受体与G蛋白偶联的机制。结果加入激动剂Apelin-13刺激后,Apelin受体与Gαi1亚基的FRET值没有发生明显的变化(P>0.05),Apelin受体与Gαi2、Gαi3亚基的FRET信号显著增加(P<0.05),而Apelin受体与Gαo、Gαq亚基的FRET信号相对于刺激前显著降低(P<0.05)。结论 Apelin受体在其激动剂Apelin-13作用下,能够激活G蛋白的Gαi2、Gαi3、Gαo、Gαq亚基,并引起Gαi2、Gαi3亚基构象重排进而与Gγ亚基相互靠近,Gαo、Gαq亚基远离Gγ2亚基,而不与Gαi1亚基发生相互作用。展开更多
基金Supported by Grants from the United States Public Health Service/National Institutes of Health, No. HL080404, HL094883 (Argraves KM) and HL061873, HL095067 (Argraves WS)NIH Training Grant to Improve Cardiovascular Therapies HL007260 (Wilkerson BA)American Heart Association 10PRE3910006 (Wilkerson BA)
文摘Blood vessels either form de novo through the process of vasculogenesis or through angiogenesis that involves the sprouting and proliferation of endothelial cells in pre-existing blood vessels. A complex interactive network of signaling cascades downstream from at least three of the nine known G-protein-coupled sphingosine-1-phosphate (S1P) receptors act as a prime effector of neovascularization that occurs in embryonic development and in association with various pathologies. This review focuses on the current knowledge of the roles of S1P signaling in vasculogenesis and angiogenesis, with particular emphasis on vascular cell adhesion and motility responses.
基金supported by a grant from the National Natural Science Foundation of China (30972920)
文摘BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those of the controls, and this phenomenon wa
文摘β-arrestin是一类重要的信号调控蛋白和支架蛋白（scaffold）。在G蛋白偶联受体（G-protein-OOU-piedreceptor，GPCR）信号转导中，β-arrestin不但可以作为GPCR信号的负性调控分子，还能作为支架蛋白促进GPCR对其他信号通路的激活，如有丝分裂原激活蛋白激酶（mitogen-activated protein kinase，MAPK）途径。另外β-arrestin还能与转录因子调节蛋白，如IKB和Mdm2相互作用问接调节NF-κB和P53介导的转录。
文摘目的探讨Apelin受体与G蛋白之间的相互作用。方法在HEK293T细胞中建立Apelin受体与各亚型G蛋白的过表达体系,利用荧光共振能量转移技术(fluorescence resonance energy transfer technology,FRET)实时、动态、连续的监测Apelin受体与G蛋白偶联的机制。结果加入激动剂Apelin-13刺激后,Apelin受体与Gαi1亚基的FRET值没有发生明显的变化(P>0.05),Apelin受体与Gαi2、Gαi3亚基的FRET信号显著增加(P<0.05),而Apelin受体与Gαo、Gαq亚基的FRET信号相对于刺激前显著降低(P<0.05)。结论 Apelin受体在其激动剂Apelin-13作用下,能够激活G蛋白的Gαi2、Gαi3、Gαo、Gαq亚基,并引起Gαi2、Gαi3亚基构象重排进而与Gγ亚基相互靠近,Gαo、Gαq亚基远离Gγ2亚基,而不与Gαi1亚基发生相互作用。
