Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs), c-Jun NH2-terminal kinases (JNKs) and p38 MAPK, play an important role in transducting environmental stimuli to the t...Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs), c-Jun NH2-terminal kinases (JNKs) and p38 MAPK, play an important role in transducting environmental stimuli to the transcriptional machinery in the nucleus in mammalian cells by virtue of their ability to phosphorylate and regulate the activity of various transcription factors. It was recently found that the changes in activity of MAPKs occurred during ischemia/reperfusion, but the biological significance of the changes was still controversial.展开更多
有丝分裂原活化蛋白激酶激酶激酶(mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3,MEKK3)是MAP3K(mitogen-activated protein kinase kinase kinase)家族的丝氨酸/苏氨酸蛋白激酶,它在哺乳...有丝分裂原活化蛋白激酶激酶激酶(mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3,MEKK3)是MAP3K(mitogen-activated protein kinase kinase kinase)家族的丝氨酸/苏氨酸蛋白激酶,它在哺乳类动物的各种组织中广泛表达。该蛋白激酶能够有效激活有丝分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)和NF-κB信号通路,与多种肿瘤的发生与发展密切相关。本文将从其结构、蛋白磷酸化、信号传导、免疫调节及与肿瘤的关系等方面对MEKK3的研究进行相关综述。展开更多
目的:研究脊髓肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)在持续性术后痛中的作用及与Toll样受体4(TLR4)/p38有丝分裂原活化蛋白激酶(p38MAPK)级联的关系。方法:选择鞘内置管成功的雄性SD大鼠120只,采用随机数字表法随机分为5组...目的:研究脊髓肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)在持续性术后痛中的作用及与Toll样受体4(TLR4)/p38有丝分裂原活化蛋白激酶(p38MAPK)级联的关系。方法:选择鞘内置管成功的雄性SD大鼠120只,采用随机数字表法随机分为5组(每组24只):假手术组、持续性术后痛组、Toll样受体4小干扰RNA组(TLR4 si RNA组)、4-(4-氟苯基)-2-(4-甲磺酰基苯基)-5-(4-吡啶基)咪唑组(SB203580组)和重组人Ⅱ型肿瘤坏死因子组(rh TNFR-Fc组)。按Flatters介绍的方法建立大鼠皮肤肌肉切口牵拉(skin/muscle incision and retraction,SMIR)持续性术后痛模型;在术前1天及术后第1、3、7、12和22天时测定大鼠机械缩足反应阈值(mechanical withdrawal threshold,MWT);按ELISA法测定脊髓TNF-α含量。结果:与术前基础值及假手术组比较,持续性术后痛组大鼠在术后第3、7、12和22天MWT明显降低(P<0.05),脊髓TNF-α含量在术后7、12和22天明显升高(P<0.05);与持续性术后痛组比较,TLR4 si RNA组和SB203580组大鼠在术后第3、7和12天,rh TNFR-Fc组在术后第7和12天MWT明显升高(P<0.05),TLR4 si RNA组、SB203580组和rh TNFR-Fc组大鼠脊髓TNF-α含量在术后第7、12和22天明显降低(P<0.05)。结论:脊髓TNF-α参与了大鼠SMIR持续性术后痛的形成,其增加与脊髓TLR4/p38MAPK级联的活化有关。展开更多
文摘Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs), c-Jun NH2-terminal kinases (JNKs) and p38 MAPK, play an important role in transducting environmental stimuli to the transcriptional machinery in the nucleus in mammalian cells by virtue of their ability to phosphorylate and regulate the activity of various transcription factors. It was recently found that the changes in activity of MAPKs occurred during ischemia/reperfusion, but the biological significance of the changes was still controversial.
文摘有丝分裂原活化蛋白激酶激酶激酶(mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3,MEKK3)是MAP3K(mitogen-activated protein kinase kinase kinase)家族的丝氨酸/苏氨酸蛋白激酶,它在哺乳类动物的各种组织中广泛表达。该蛋白激酶能够有效激活有丝分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)和NF-κB信号通路,与多种肿瘤的发生与发展密切相关。本文将从其结构、蛋白磷酸化、信号传导、免疫调节及与肿瘤的关系等方面对MEKK3的研究进行相关综述。
文摘目的:研究脊髓肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)在持续性术后痛中的作用及与Toll样受体4(TLR4)/p38有丝分裂原活化蛋白激酶(p38MAPK)级联的关系。方法:选择鞘内置管成功的雄性SD大鼠120只,采用随机数字表法随机分为5组(每组24只):假手术组、持续性术后痛组、Toll样受体4小干扰RNA组(TLR4 si RNA组)、4-(4-氟苯基)-2-(4-甲磺酰基苯基)-5-(4-吡啶基)咪唑组(SB203580组)和重组人Ⅱ型肿瘤坏死因子组(rh TNFR-Fc组)。按Flatters介绍的方法建立大鼠皮肤肌肉切口牵拉(skin/muscle incision and retraction,SMIR)持续性术后痛模型;在术前1天及术后第1、3、7、12和22天时测定大鼠机械缩足反应阈值(mechanical withdrawal threshold,MWT);按ELISA法测定脊髓TNF-α含量。结果:与术前基础值及假手术组比较,持续性术后痛组大鼠在术后第3、7、12和22天MWT明显降低(P<0.05),脊髓TNF-α含量在术后7、12和22天明显升高(P<0.05);与持续性术后痛组比较,TLR4 si RNA组和SB203580组大鼠在术后第3、7和12天,rh TNFR-Fc组在术后第7和12天MWT明显升高(P<0.05),TLR4 si RNA组、SB203580组和rh TNFR-Fc组大鼠脊髓TNF-α含量在术后第7、12和22天明显降低(P<0.05)。结论:脊髓TNF-α参与了大鼠SMIR持续性术后痛的形成,其增加与脊髓TLR4/p38MAPK级联的活化有关。
