Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase...Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.展开更多
Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation ...Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.展开更多
We established a rat model of cardiac arrest by clamping the endotracheal tube of adult rats at expiration. Twenty-four hours after cardiopulmonary resuscitation, nerve cell injury and expression of tumor necrosis fac...We established a rat model of cardiac arrest by clamping the endotracheal tube of adult rats at expiration. Twenty-four hours after cardiopulmonary resuscitation, nerve cell injury and expression of tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase content were increased. Rats injected with Xuebijing, a Chinese herb compound preparation, exhibited normal cellular structure and morphology, dense neuronal cytoplasm, and decreased tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase expression at 24 hours following cardiopulmonary resuscitation. These data suggest that Xuebijing can attenuate neuronal injury induced by hypoxia and reperfusion during cardiopulmonary resuscitation.展开更多
【目的】观察髓核源性坐骨神经痛大鼠模型中背根神经节磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)表达的变化及其与炎性反应和机械痛敏的关系,以探讨腰椎间盘突出症的病理机制。【方法】选择成年SD雄性大鼠66只随机分为空白组(12只)、假...【目的】观察髓核源性坐骨神经痛大鼠模型中背根神经节磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)表达的变化及其与炎性反应和机械痛敏的关系,以探讨腰椎间盘突出症的病理机制。【方法】选择成年SD雄性大鼠66只随机分为空白组(12只)、假手术组(18只)和模型组(36只)。模型组在左腰5神经背根神经节(L5DRG)自体髓核移植以建立大鼠非压迫性腰椎间盘突出模型,假手术组自体肌肉移植。空白组不进行手术。测量各组大鼠术前至术后21 d的左后肢50%机械性撤足阈值(50%PWT)以测定机械痛敏的变化,空白组、假手术组术后7 d及模型组术后7、14、21 d各12只大鼠取左腰5DRG用免疫组化法测定环氧化酶-2(COX-2)与p-p38MAPK的阳性细胞比率。【结果】假手术组50%PWT术后无明显变化,模型组术后7 d出现明显的50%PWT下降损伤,术后14 d达最低值,术后21 d部分恢复;空白组、假手术组术后7 dDRG的COX-2和p-p38MAPK微弱表达,模型组术后7 d DRG的COX-2和p-p38MAPK高表达,模型组术后14 d DRG的COX-2和p-p38MAPK表达更高,模型组术后21 d DRG的COX-2和p-p38MAPK表达减弱。【结论】背根神经节的p-p38MAPK的表达与非压迫性髓核所致炎性反应和坐骨神经病理性神经痛的变化密切相关。展开更多
目的观察p38蛋白激酶(p38mitogen-activated protein kinase,p38MAPK)在癫大鼠脑内的表达情况。方法健康雄性SD大鼠随机分成正常对照组(n=8)和癫组(n=8)。采用戊四氮腹腔注射建立癫模型,大鼠点燃后的惊厥行为按照Racine的标准进...目的观察p38蛋白激酶(p38mitogen-activated protein kinase,p38MAPK)在癫大鼠脑内的表达情况。方法健康雄性SD大鼠随机分成正常对照组(n=8)和癫组(n=8)。采用戊四氮腹腔注射建立癫模型,大鼠点燃后的惊厥行为按照Racine的标准进行观察评分,采用Western blot和免疫荧光法比较两组大鼠脑内p38MAPK的表达情况。结果癫组大鼠脑内p38MAPK在皮层和海马的表达均显著高于正常对照组(P<0.01)。结论 p38MAPK在癫大鼠脑内表达上调。展开更多
Curcumin, as a main pharmacological component in the traditional Chinese medicine-- tttrmeric, has shown anti-inflammatory, anti-oxidation, anti-tumor and anti-fibrotic effects. This study aimed to investigate the pos...Curcumin, as a main pharmacological component in the traditional Chinese medicine-- tttrmeric, has shown anti-inflammatory, anti-oxidation, anti-tumor and anti-fibrotic effects. This study aimed to investigate the possible underlying signaling pathway which was involved in the inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin. Rat mesangial cells in vitro were incubated with low-density lipoprotein （LDL） and different concentrations of curcumin （0, 6.25, 12.5, 25.0 9mol/L） or p38 MAPK inhibitor, SB203580 （10 μmol/L）. Under LDL incubation, mesangial cells proliferated, the expression of MMP-2 mRNA and protein was decreased, the expression of COX-2 mRNA and protein was increased, reactive oxygen species （ROS） generation was increased and p38 MAPK was activated significantly （P〈0.05）. When LDL-induced cells were treated with curcumin in the concentration of 12.5 or 25.0 μmol/L, LDL-induced proliferation ofmesangial cells was suppressed, the expression of MMP-2 mRNA and protein increased, the expression of COX-2 mRNA and protein downregulated, the production of ROS inhibited and p38 MAPK inactivated （P〈0.05）. In conclusion, curcumin can inhibit the LDL-induced proliferation of mesangial cells and up-regulate the expression of MMP-2, which may be related with the inhibitory effect of curcumin on COX-2 expression, ROS pro- duction and p38 MAPK.展开更多
Ninety male Wistar rats were selected under the ＂Guide for the Care and Use of Laboratory Animals＂ for skin-muscle wound models. Three groups of animals were examined respectively for inoculation of inhibitor of p38...Ninety male Wistar rats were selected under the ＂Guide for the Care and Use of Laboratory Animals＂ for skin-muscle wound models. Three groups of animals were examined respectively for inoculation of inhibitor of p38 MAPK （mitogen activated protein kinase） SB 203580 and JNK inhibitor SP 600125, and a control. Light microscopy, immunohistochemistry, and tensometry revealed that the inhibition of p38 or JNK cascades have modified the formation of the connective tissue scar. The degree of connective tissue growth in the area of surgical wound had been significantly reduced by the end of observation （30 d） as the SB 203580 was applied （% volume of collagen 43.60 （41.05 - 60.15） vs. 73.54 （66.87 - 78.01） in control, p = 0.002）. Conversely, when we have applied the JNK blocker, the density of collagen in scar tissue increased （78.14 （72.77 - 81.14）, p = 0.022 vs. control）. SB203580 inhibits the expression of p38, c-Jun and c-Fos. When we have used the JNK blocker, the expression of c-Fos and c-Jun decreased, but the expression of p38 increased. This determines the high functional activity of fibroblasts after using SP 600125. Obtained results show the importance of studying regulators of cell differentiation as potential drugs, which significantly affect the outcome of the pathological processes.展开更多
Background The plasma concentration of very low density lipoprotein （VLDL） is negatively correlated to renal function in glomerular diseases. Effects of VLDL on renal function have been partially attributed to the p...Background The plasma concentration of very low density lipoprotein （VLDL） is negatively correlated to renal function in glomerular diseases. Effects of VLDL on renal function have been partially attributed to the proliferation of mesangial cells. This study examined the potential role of the p42/44 mitogen activated protein kinase （MAPK） in mesangial cell proliferation induced by VLDL. Methods Mesangial cells were treated with VLDL at different concentrations or for different time. The cell cycle of the mesangial cells was analyzed by Xl-r assay and flow-cytometry; MAPK activity was also assayed. In some experiments, cells were treated with VLDL together with or without 0.1 pmol/L PD 98059. Results Ten to 500 μg/ml VLDL stimulated the proliferation of mesangial cells cultured in vitro in a concentration-dependent manner. The effect was associated with an increase in p42/44 MAPK activity. Increased proliferation of mesangial cells by VLDL was significantly attenuated by PD98059, a specific p42/44 MAPK inhibitor. Conclusion These results indicate that the p42/44 MAPK pathway is an important regulator of mesangial cell proliferation and of renal functions.展开更多
基金supported in part by grants from the Young Scientists Awards Foundation of Shandong Province of China,No.BS2013YY049the China Postdoctoral Science Foundation,No.2012M511036
文摘Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.
文摘Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.
基金a grant from the Science and Technology Department of Jilin Province,No. 200705172
文摘We established a rat model of cardiac arrest by clamping the endotracheal tube of adult rats at expiration. Twenty-four hours after cardiopulmonary resuscitation, nerve cell injury and expression of tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase content were increased. Rats injected with Xuebijing, a Chinese herb compound preparation, exhibited normal cellular structure and morphology, dense neuronal cytoplasm, and decreased tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase expression at 24 hours following cardiopulmonary resuscitation. These data suggest that Xuebijing can attenuate neuronal injury induced by hypoxia and reperfusion during cardiopulmonary resuscitation.
文摘【目的】观察髓核源性坐骨神经痛大鼠模型中背根神经节磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)表达的变化及其与炎性反应和机械痛敏的关系,以探讨腰椎间盘突出症的病理机制。【方法】选择成年SD雄性大鼠66只随机分为空白组(12只)、假手术组(18只)和模型组(36只)。模型组在左腰5神经背根神经节(L5DRG)自体髓核移植以建立大鼠非压迫性腰椎间盘突出模型,假手术组自体肌肉移植。空白组不进行手术。测量各组大鼠术前至术后21 d的左后肢50%机械性撤足阈值(50%PWT)以测定机械痛敏的变化,空白组、假手术组术后7 d及模型组术后7、14、21 d各12只大鼠取左腰5DRG用免疫组化法测定环氧化酶-2(COX-2)与p-p38MAPK的阳性细胞比率。【结果】假手术组50%PWT术后无明显变化,模型组术后7 d出现明显的50%PWT下降损伤,术后14 d达最低值,术后21 d部分恢复;空白组、假手术组术后7 dDRG的COX-2和p-p38MAPK微弱表达,模型组术后7 d DRG的COX-2和p-p38MAPK高表达,模型组术后14 d DRG的COX-2和p-p38MAPK表达更高,模型组术后21 d DRG的COX-2和p-p38MAPK表达减弱。【结论】背根神经节的p-p38MAPK的表达与非压迫性髓核所致炎性反应和坐骨神经病理性神经痛的变化密切相关。
文摘目的观察p38蛋白激酶(p38mitogen-activated protein kinase,p38MAPK)在癫大鼠脑内的表达情况。方法健康雄性SD大鼠随机分成正常对照组(n=8)和癫组(n=8)。采用戊四氮腹腔注射建立癫模型,大鼠点燃后的惊厥行为按照Racine的标准进行观察评分,采用Western blot和免疫荧光法比较两组大鼠脑内p38MAPK的表达情况。结果癫组大鼠脑内p38MAPK在皮层和海马的表达均显著高于正常对照组(P<0.01)。结论 p38MAPK在癫大鼠脑内表达上调。
文摘目的:研究P38丝裂原活化蛋白激酶(mitogenactivated protein kinase,MAPK)通路在急性重症胰腺炎(severe acute pancreatitis,SAP)大鼠模型海马神经元中对诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)和前列腺素E2(prostaglandin E2,PGE2)的作用.方法:将60只SD大鼠随机分为对照组、SAP模型组(模型组)、抑制剂组(P38MAPK通路抑制剂SB203580).Nissl染色、免疫组织化学显色、免疫印迹法检测大鼠海马CA1区iNOS、PGE2和p-P38表达的变化;应用透射电镜观察胰腺组织超微结构的变化.结果:与对照组相比,SAP模型组海马CA1区p-P38(20.4±2.2 vs 2.1±1.3)、i NOS(33.6±4.4 vs 3.7±0.4)、PGE2(34.7±4.0 vs 2.4±1.0)阳性神经元的数量显著增加(P<0.05);给予S B203580后,抑制剂组海马C A1区p-P3 8(1 2.8±0.7)、iNOS(1 4.4±4.9)、P G E2(18.3±0.5)阳性神经元的数量明显减少(P<0.05).模型组胰腺细胞粗面内质网脱颗粒,线粒体水肿扩张,抑制剂组上述改变明显减轻.结论:P38丝裂原活化蛋白激酶通路对SAP大鼠模型海马i NOS和PGE2表达可能起调控作用,抑制该通路对SAP大鼠具有神经保护作用.
基金supported by grants from the National Natural Science Foundation of China(No.81100485)Scientific Research Foundation for Returned Scholars, Ministry of Education of China(No.[2011]1568)
文摘Curcumin, as a main pharmacological component in the traditional Chinese medicine-- tttrmeric, has shown anti-inflammatory, anti-oxidation, anti-tumor and anti-fibrotic effects. This study aimed to investigate the possible underlying signaling pathway which was involved in the inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin. Rat mesangial cells in vitro were incubated with low-density lipoprotein （LDL） and different concentrations of curcumin （0, 6.25, 12.5, 25.0 9mol/L） or p38 MAPK inhibitor, SB203580 （10 μmol/L）. Under LDL incubation, mesangial cells proliferated, the expression of MMP-2 mRNA and protein was decreased, the expression of COX-2 mRNA and protein was increased, reactive oxygen species （ROS） generation was increased and p38 MAPK was activated significantly （P〈0.05）. When LDL-induced cells were treated with curcumin in the concentration of 12.5 or 25.0 μmol/L, LDL-induced proliferation ofmesangial cells was suppressed, the expression of MMP-2 mRNA and protein increased, the expression of COX-2 mRNA and protein downregulated, the production of ROS inhibited and p38 MAPK inactivated （P〈0.05）. In conclusion, curcumin can inhibit the LDL-induced proliferation of mesangial cells and up-regulate the expression of MMP-2, which may be related with the inhibitory effect of curcumin on COX-2 expression, ROS pro- duction and p38 MAPK.
文摘Ninety male Wistar rats were selected under the ＂Guide for the Care and Use of Laboratory Animals＂ for skin-muscle wound models. Three groups of animals were examined respectively for inoculation of inhibitor of p38 MAPK （mitogen activated protein kinase） SB 203580 and JNK inhibitor SP 600125, and a control. Light microscopy, immunohistochemistry, and tensometry revealed that the inhibition of p38 or JNK cascades have modified the formation of the connective tissue scar. The degree of connective tissue growth in the area of surgical wound had been significantly reduced by the end of observation （30 d） as the SB 203580 was applied （% volume of collagen 43.60 （41.05 - 60.15） vs. 73.54 （66.87 - 78.01） in control, p = 0.002）. Conversely, when we have applied the JNK blocker, the density of collagen in scar tissue increased （78.14 （72.77 - 81.14）, p = 0.022 vs. control）. SB203580 inhibits the expression of p38, c-Jun and c-Fos. When we have used the JNK blocker, the expression of c-Fos and c-Jun decreased, but the expression of p38 increased. This determines the high functional activity of fibroblasts after using SP 600125. Obtained results show the importance of studying regulators of cell differentiation as potential drugs, which significantly affect the outcome of the pathological processes.
文摘Background The plasma concentration of very low density lipoprotein （VLDL） is negatively correlated to renal function in glomerular diseases. Effects of VLDL on renal function have been partially attributed to the proliferation of mesangial cells. This study examined the potential role of the p42/44 mitogen activated protein kinase （MAPK） in mesangial cell proliferation induced by VLDL. Methods Mesangial cells were treated with VLDL at different concentrations or for different time. The cell cycle of the mesangial cells was analyzed by Xl-r assay and flow-cytometry; MAPK activity was also assayed. In some experiments, cells were treated with VLDL together with or without 0.1 pmol/L PD 98059. Results Ten to 500 μg/ml VLDL stimulated the proliferation of mesangial cells cultured in vitro in a concentration-dependent manner. The effect was associated with an increase in p42/44 MAPK activity. Increased proliferation of mesangial cells by VLDL was significantly attenuated by PD98059, a specific p42/44 MAPK inhibitor. Conclusion These results indicate that the p42/44 MAPK pathway is an important regulator of mesangial cell proliferation and of renal functions.
