目的探究血管紧张素(1-7)[angiotensin-(1-7),Ang-(1-7)]及线粒体组装受体(mitochondrial assembly of receptor,MasR)在子宫内膜癌中的表达及相关性。方法选取河北北方学院附属第一医院2017年4月~2019年4月治疗的16例正常子宫内膜组织...目的探究血管紧张素(1-7)[angiotensin-(1-7),Ang-(1-7)]及线粒体组装受体(mitochondrial assembly of receptor,MasR)在子宫内膜癌中的表达及相关性。方法选取河北北方学院附属第一医院2017年4月~2019年4月治疗的16例正常子宫内膜组织,32例子宫内膜不典型增生组织和78例手术切除的子宫内膜癌组织,共126例。使用酶联免疫吸附法(ELISA)检测Ang-(1-7),Western blot检测MasR在组织中的表达情况。结果三组组织中,正常子宫内膜组织内Ang-(1-7)(χ^(2)=11.506,P=0.000)和MasR(χ^(2)=8.619,P=0.002)阳性率最低,子宫内膜癌组阳性率最高,差异均具有统计学意义。与另外两组相比,子宫内膜癌组Ang-(1-7)和MasR表达显著增高。Ang-(1-7),MasR表达水平和子宫内膜癌肿瘤分期(t≥2.82,P=0.001)、转移(F=33.35和13.80,P=0.000)及分化程度(t≥2.82,P=0.029)均有相关性。结论Ang-(1-7)及MasR参与了子宫内膜癌新生血管的生成,其表达增高可促发癌细胞增长,可用于治疗及预后子宫内膜癌的新靶点。展开更多
Objective To investigate effect of pinacidil, an ATP sensitive potassium channel （KATP） opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rat...Objective To investigate effect of pinacidil, an ATP sensitive potassium channel （KATP） opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rats. Methods One hundred male Wistar rats were randomly divided into four groups： A, sham-operated group; B, ischemia-reperfusion group; C, KATe opener treatment group; and D, KATe opener and blocker treatment group. The middle cerebral artery occlusion （MCAO） model was established by using the intraluminal suture occlusion method, neuronal apoptosis was determined by TUNEL staining, and expressions of caspase-8, caspase-9 and caspase-3 mRNA were detected by in situ hybridization. Results （1） The numbers of apoptotic neurons at 12 h, 24 h, 48 h, and 72 h were significantly less in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there was no difference between groups B and D at all time points （P 〉 0.05）. （2） The expressions of caspase-3 mRNA and caspase-8 mRNA at all times and the expressions of caspase-9 mRNA at 12 h, 24 h, 48 h, 72 h were significantly lower in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there were no differences between groups B and D at all time points （P 〉 0.05）. Conclusions KATP opener can significantly decrease the neuronal apoptosis and the expressions of caspase-3, caspase-8 and caspase-9 mRNAs following cerebral ischemiareperfusion. The neuronal apoptosis may be decreased by the inhibition of both mitochondrial and death-receptor signal pathways.展开更多
LIGHT [homologous to lymphotoxins, shows inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM/TR2)] is a new member of TNF superfamily. The HT-29 colon canc...LIGHT [homologous to lymphotoxins, shows inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM/TR2)] is a new member of TNF superfamily. The HT-29 colon cancer cell line is the most sensitive to LIGHT-induced, IFNγ-mediated apoptosis among the cell lines we have examined so far. Besides downregulation of Bcl-XL, upregulation of Bak, and activation of both PARP [poly (ADP-ribose)polymerase] and DFF45 (DNA fragmentation factor), LIGHT-induced, IFNγ-mediated apoptosis of HT-29 cells involves extensive caspase activation. Caspase-8 and caspase-9 activation, as shown by their cleavages appeared as early as 24 h after treatment, whereas caspase-3 and caspase-7 activation, as shown by their cleavages occurred after 72 h of LIGHT treatment. Caspase-3 inhibitor Z-DEVD-FMK (benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone)and a broad range caspase inhibitor Z-VAD-FMK (benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone) were able to block LIGHT-induced, IFNγ-mediated apoptosis of HT-29 cells. The activity of caspase-3, which is one of the major executioner caspases, was found to be inhibited by both Z-DEVD-MFK and Z-VAD-FMK. These results suggest that LIGHT-induced, IFNγ-mediated apoptosis of HT-29 cells is caspase-dependent, and LIGHT signaling is mediated through both death receptor and mitochondria pathways.展开更多
Apoptosis is a complex process involving a large array of genes and mutation of any of these genes may lead to malignancy formation. Re-acquirement of FasL by tumor cells may enable them to evade the surveillance of i...Apoptosis is a complex process involving a large array of genes and mutation of any of these genes may lead to malignancy formation. Re-acquirement of FasL by tumor cells may enable them to evade the surveillance of immune system and thus contributes to the growth of tumor. Apart from traditional therapies, inducing apoptosis of tumor cell by new methods employing death receptor ligands and making use of Fas counterattack is also being developed.展开更多
Two major apoptosis pathways have been defined in mammalian cells, the Fas/TNF-R1 death receptor pathway and the mitochondria pathway. The Bcl-2 family proteins consist of both anti-apoptosis and pro- apoptosis member...Two major apoptosis pathways have been defined in mammalian cells, the Fas/TNF-R1 death receptor pathway and the mitochondria pathway. The Bcl-2 family proteins consist of both anti-apoptosis and pro- apoptosis members that regulate apoptosis, mainly by controlling the release of cytochrome c and other mitochondrial apoptotic events. However, death signals mediated by Fas/TNF-R1 receptors can usually activate caspases directly, bypassing the need for mitochondria and escaping the regulation by Bcl-2 family proteins. Bid is a novel pro-apoptosis Bcl-2 family protein that is activated by caspase 8 in response to Fas/TNF-R1 death receptor signals. Activated Bid is translocated to mitochondria and induces cytochrome c release, which in turn activates downstream caspases. Such a connection between the two apoptosis pathways could be important for induction of apoptosis in certain types of cells and responsible for the pathogenesis of a number of human diseases.展开更多
文摘目的探究血管紧张素(1-7)[angiotensin-(1-7),Ang-(1-7)]及线粒体组装受体(mitochondrial assembly of receptor,MasR)在子宫内膜癌中的表达及相关性。方法选取河北北方学院附属第一医院2017年4月~2019年4月治疗的16例正常子宫内膜组织,32例子宫内膜不典型增生组织和78例手术切除的子宫内膜癌组织,共126例。使用酶联免疫吸附法(ELISA)检测Ang-(1-7),Western blot检测MasR在组织中的表达情况。结果三组组织中,正常子宫内膜组织内Ang-(1-7)(χ^(2)=11.506,P=0.000)和MasR(χ^(2)=8.619,P=0.002)阳性率最低,子宫内膜癌组阳性率最高,差异均具有统计学意义。与另外两组相比,子宫内膜癌组Ang-(1-7)和MasR表达显著增高。Ang-(1-7),MasR表达水平和子宫内膜癌肿瘤分期(t≥2.82,P=0.001)、转移(F=33.35和13.80,P=0.000)及分化程度(t≥2.82,P=0.029)均有相关性。结论Ang-(1-7)及MasR参与了子宫内膜癌新生血管的生成,其表达增高可促发癌细胞增长,可用于治疗及预后子宫内膜癌的新靶点。
文摘Objective To investigate effect of pinacidil, an ATP sensitive potassium channel （KATP） opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rats. Methods One hundred male Wistar rats were randomly divided into four groups： A, sham-operated group; B, ischemia-reperfusion group; C, KATe opener treatment group; and D, KATe opener and blocker treatment group. The middle cerebral artery occlusion （MCAO） model was established by using the intraluminal suture occlusion method, neuronal apoptosis was determined by TUNEL staining, and expressions of caspase-8, caspase-9 and caspase-3 mRNA were detected by in situ hybridization. Results （1） The numbers of apoptotic neurons at 12 h, 24 h, 48 h, and 72 h were significantly less in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there was no difference between groups B and D at all time points （P 〉 0.05）. （2） The expressions of caspase-3 mRNA and caspase-8 mRNA at all times and the expressions of caspase-9 mRNA at 12 h, 24 h, 48 h, 72 h were significantly lower in group C than in groups B and D （P 〈 0.01 or P 〈 0.05）; and there were no differences between groups B and D at all time points （P 〉 0.05）. Conclusions KATP opener can significantly decrease the neuronal apoptosis and the expressions of caspase-3, caspase-8 and caspase-9 mRNAs following cerebral ischemiareperfusion. The neuronal apoptosis may be decreased by the inhibition of both mitochondrial and death-receptor signal pathways.
文摘LIGHT [homologous to lymphotoxins, shows inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM/TR2)] is a new member of TNF superfamily. The HT-29 colon cancer cell line is the most sensitive to LIGHT-induced, IFNγ-mediated apoptosis among the cell lines we have examined so far. Besides downregulation of Bcl-XL, upregulation of Bak, and activation of both PARP [poly (ADP-ribose)polymerase] and DFF45 (DNA fragmentation factor), LIGHT-induced, IFNγ-mediated apoptosis of HT-29 cells involves extensive caspase activation. Caspase-8 and caspase-9 activation, as shown by their cleavages appeared as early as 24 h after treatment, whereas caspase-3 and caspase-7 activation, as shown by their cleavages occurred after 72 h of LIGHT treatment. Caspase-3 inhibitor Z-DEVD-FMK (benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone)and a broad range caspase inhibitor Z-VAD-FMK (benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone) were able to block LIGHT-induced, IFNγ-mediated apoptosis of HT-29 cells. The activity of caspase-3, which is one of the major executioner caspases, was found to be inhibited by both Z-DEVD-MFK and Z-VAD-FMK. These results suggest that LIGHT-induced, IFNγ-mediated apoptosis of HT-29 cells is caspase-dependent, and LIGHT signaling is mediated through both death receptor and mitochondria pathways.
文摘Apoptosis is a complex process involving a large array of genes and mutation of any of these genes may lead to malignancy formation. Re-acquirement of FasL by tumor cells may enable them to evade the surveillance of immune system and thus contributes to the growth of tumor. Apart from traditional therapies, inducing apoptosis of tumor cell by new methods employing death receptor ligands and making use of Fas counterattack is also being developed.
文摘Two major apoptosis pathways have been defined in mammalian cells, the Fas/TNF-R1 death receptor pathway and the mitochondria pathway. The Bcl-2 family proteins consist of both anti-apoptosis and pro- apoptosis members that regulate apoptosis, mainly by controlling the release of cytochrome c and other mitochondrial apoptotic events. However, death signals mediated by Fas/TNF-R1 receptors can usually activate caspases directly, bypassing the need for mitochondria and escaping the regulation by Bcl-2 family proteins. Bid is a novel pro-apoptosis Bcl-2 family protein that is activated by caspase 8 in response to Fas/TNF-R1 death receptor signals. Activated Bid is translocated to mitochondria and induces cytochrome c release, which in turn activates downstream caspases. Such a connection between the two apoptosis pathways could be important for induction of apoptosis in certain types of cells and responsible for the pathogenesis of a number of human diseases.
