This review summarized our recent studies on involvement of tissue type plasminogen activator(tPA)and plasminogen activator inhibitor type 1(PAI-1) in process of ovulation.We have demonstrated that 1)hCG induces ovula...This review summarized our recent studies on involvement of tissue type plasminogen activator(tPA)and plasminogen activator inhibitor type 1(PAI-1) in process of ovulation.We have demonstrated that 1)hCG induces ovulation and coordinated tPA and PAI-1 gene expression in both rat and monkey ovaries;(2) GnRH and FSH are also capable of inducing ovulation by increasing ovarian tPA and PAI-1 gene expression in the same manner as hCG does;(3)Compounds which increase tPA production can induce oviation while compounds which decrease tPA and/or increase PAI-1 expression inhibit ovulation. Based on the data provided,a working model on the involvement of tPA in ovulation is presented.展开更多
Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator（t PA） from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes t...Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator（t PA） from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes the exocytosis and subsequent endocytic retrieval of glutamate-containing synaptic vesicles,and regulates the postsynaptic response to the presynaptic release of glutamate.Indeed,t PA has a bidirectional effect on the composition of the postsynaptic density（PSD） that does not require plasmin generation or the presynaptic release of glutamate,but varies according to the baseline level of neuronal activity.Hence,in inactive neurons t PA induces phosphorylation and accumulation in the PSD of the Ca^（2＋）/calmodulin-dependent protein kinase IIα（pCa MKIIα）,followed by pCa MKIIα-induced phosphorylation and synaptic recruitment of Glu R1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid（AMPA） receptors.In contrast,in active neurons with increased levels of pCa MKIIα in the PSD t PA induces pCa MKIIα and p Glu R1 dephosphorylation and their subsequent removal from the PSD.These effects require active synaptic N-methyl-D-aspartate（NMDA） receptors and cyclin-dependent kinase 5（Cdk5）-induced phosphorylation of the protein phosphatase 1（PP1） at T320.These data indicate that t PA is a homeostatic regulator of the postsynaptic response of cerebral cortical neurons to the presynaptic release of glutamate via bidirectional regulation of the pCa MKIIα/PP1 switch in the PSD.展开更多
文摘This review summarized our recent studies on involvement of tissue type plasminogen activator(tPA)and plasminogen activator inhibitor type 1(PAI-1) in process of ovulation.We have demonstrated that 1)hCG induces ovulation and coordinated tPA and PAI-1 gene expression in both rat and monkey ovaries;(2) GnRH and FSH are also capable of inducing ovulation by increasing ovarian tPA and PAI-1 gene expression in the same manner as hCG does;(3)Compounds which increase tPA production can induce oviation while compounds which decrease tPA and/or increase PAI-1 expression inhibit ovulation. Based on the data provided,a working model on the involvement of tPA in ovulation is presented.
基金supported in part by National Institutes of Health Grants NS-079331(to MY)and NS-091201(to MY)
文摘Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator（t PA） from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes the exocytosis and subsequent endocytic retrieval of glutamate-containing synaptic vesicles,and regulates the postsynaptic response to the presynaptic release of glutamate.Indeed,t PA has a bidirectional effect on the composition of the postsynaptic density（PSD） that does not require plasmin generation or the presynaptic release of glutamate,but varies according to the baseline level of neuronal activity.Hence,in inactive neurons t PA induces phosphorylation and accumulation in the PSD of the Ca^（2＋）/calmodulin-dependent protein kinase IIα（pCa MKIIα）,followed by pCa MKIIα-induced phosphorylation and synaptic recruitment of Glu R1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid（AMPA） receptors.In contrast,in active neurons with increased levels of pCa MKIIα in the PSD t PA induces pCa MKIIα and p Glu R1 dephosphorylation and their subsequent removal from the PSD.These effects require active synaptic N-methyl-D-aspartate（NMDA） receptors and cyclin-dependent kinase 5（Cdk5）-induced phosphorylation of the protein phosphatase 1（PP1） at T320.These data indicate that t PA is a homeostatic regulator of the postsynaptic response of cerebral cortical neurons to the presynaptic release of glutamate via bidirectional regulation of the pCa MKIIα/PP1 switch in the PSD.
文摘目的探索阿替普酶治疗急性缺血性脑卒中的疗效和影响急性缺血性脑卒中静脉溶栓预后的因素,积极干预相关因素,提高静脉溶栓治疗的效率。方法随机抽取急性缺血性脑卒中患者120例,入组患者注射阿替普酶行静脉溶栓治疗,在静脉溶栓后24 h和3个月,分别采用美国国立卫生研究院卒中量表(NIHSS)评分和改良神经功能量表(mRS)评分评价神经功能的改善程度和预后,应用Logistic回归分析影响急性缺血性脑卒中患者溶栓治疗预后的危险因素。结果静脉溶栓后24 h预后良好的有84例(70.0%),恢复不良的有36例(30.0%);静脉溶栓后24 h NIHSS评分为(11.23±0.68)分,较溶栓前的(16.11±1.32)分明显降低(P<0.05)。静脉溶栓后3个月预后良好有70例(58.3%),预后不良为50例(41.7%);静脉溶栓后3个月mRS评分为(2.10±0.18)分,较溶栓前的(3.14±0.41)分明显降低(P<0.05)。Logistic回归分析显示,脂蛋白A1/B比值、发病至入院时间(OTD)、入院至溶栓时间(DTN)、NIHSS评分、高尿酸水平和高同型半胱氨酸(Hcy)的OR值分别为1.012、1.679、1.435、1.457、0.305、1.201,P值分别为0.011、0.007、0.032、0.004、0.005、0.015。结论阿替普酶治疗急性缺血性脑卒中疗效显著,脂蛋白A1/B比值、OTD、DTN、NIHSS评分、高尿酸水平和Hcy血症是影响预后的危险因素。
