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Electroacupuncture reduces apoptotic index and inhibits p38 mitogen-activated protein kinase signaling pathway in the hippocampus of rats with cerebral ischemia/reperfusion injury 被引量:18
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作者 Xiao Lan Xin Zhang +3 位作者 Guo-ping Zhou Chun-xiao Wu Chun Li Xiu-hong Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第3期409-416,共8页
Electroacupuncture attenuates cerebral hypoxia and neuronal apoptosis induced by cerebral ischemia/reperfusion injury.To further identify the involved mechanisms,we assumed that electroacupuncture used to treat cerebr... Electroacupuncture attenuates cerebral hypoxia and neuronal apoptosis induced by cerebral ischemia/reperfusion injury.To further identify the involved mechanisms,we assumed that electroacupuncture used to treat cerebral ischemia/reperfusion injury was associated with the p38 mitogen-activated protein kinase(MAPK) signaling pathway.We established rat models of cerebral ischemia/reperfusion injury using the modified Zea-Longa's method.At 30 minutes before model establishment,p38 MAPK blocker SB20358 was injected into the left lateral ventricles.At 1.5 hours after model establishment,electroacupuncture was administered at acupoints of Chize(LU5),Hegu(LI4),Zusanli(ST36),and Sanyinjiao(SP6) for 20 minutes in the affected side.Results showed that the combination of EA and SB20358 injection significantly decreased neurologic impairment scores,but no significant differences were determined among different interventional groups.Hematoxylin-eosin staining also showed reduced brain tissue injuries.Compared with the SB20358 group,the cells were regularly arranged,the structures were complete,and the number of viable neurons was higher in the SB20358 + electroacupuncture group.Terminal deoxynucleotidyl transferase(Td T)-mediated d UTP nick-end labeling assay showed a decreased apoptotic index in each group,with a significant decrease in the SB20358 + electroacupuncture group.Immunohistochemistry revealed reduced phosphorylated p38 expression at 3 days in the electroacupuncture group and SB20358 + electroacupuncture group compared with the ischemia/reperfusion group.There was no significant difference in phosphorylated p38 expression between the ischemia/reperfusion group and SB20358 group.These findings confirmed that the electroacupuncture effects on mitigating cerebral ischemia/reperfusion injury are possibly associated with the p38 MAPK signaling pathway.A time period of 3 days could promote the repair of ischemic cerebral nerves. 展开更多
关键词 nerve regeneration brain injury ELECTROACUpUNCTURE cell apoptosis cerebral ischemia/reperfusion injury neurological impairment score morphological changes immunohistoehemical assay p38 mitogen-activated protein kinases phosphorylated p38 HIppOCAMpUS neural regeneration
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Activation and signaling of the p38 MAP kinase pathway 被引量:152
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作者 Tyler ZARUBIN 《Cell Research》 SCIE CAS CSCD 2005年第1期11-18,共8页
The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve... The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38. 展开更多
关键词 p38 MAp kinase signaling pathway NEXUS inflammation DIFFERENTIATION SENESCENCE tumorigenesis.
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Inhibition of p38 mitogen-activated protein kinase may decrease intestinal epithelial cell apoptosis and improve intestinal epithelial barrier function after ischemia- reperf usion injury 被引量:8
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作者 Shu-YunZheng Xiao-BingFu +3 位作者 Jian-GuoXu Jing-YuZhao Tong-ZhuSun WeiChen 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第5期656-660,共5页
AIM: To investigate the role of p38 mitogen-activated protein kinase in rat small intestine after ischemia-reperfusion (I/R)insult and the relationship between activation of p38 MAPK and apoptotic cell death of intest... AIM: To investigate the role of p38 mitogen-activated protein kinase in rat small intestine after ischemia-reperfusion (I/R)insult and the relationship between activation of p38 MAPK and apoptotic cell death of intestine.METHODS: Ninety Wistar rats were divided randomly into three groups, namely sham-operated group (C), I/R vehicle group (R) and SB203580 pre-treated group(S).In groups R and S, the superior mesenteric artery(SMA)was separated and occluded for 45 min, then released for reperfusion for0.25, 0.5, 1, 2, 6, 12 and 24 h. In group C, SMA was separated without occlusion. Plasma D-lactate levels were examined and histological changes were observed under a light microscope. The activity of p38 MAPK was determined by Western immunoblotting and apoptotic cells were detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUDP-biotin nick end labeling (TUNEL).RESULTS: Intestinal ischemia followed by reperfusion activated p38 MAPK, and the maximal level of activation (7.3-fold vs sham-operated group) was reached 30 min after I/R. Treatment with SB 203580, a p38 MAPK inhibitor,reduced intestinal apoptosis (26.72±3.39% vs62.50±3.08%in I/R vehicle, P<0.01) and decreased plasma D-lactate level (0.78±0.15 mmol/L in I/R vehicle vs0.42±0.17 mmol/L in SB-treated group) and improved post-ischemic intestinal histological damage.CONCLUSION: p38 MAPK plays a crucial role in the signal transduction pathway mediating post-ischemic intestinal apoptosis, and inhibition of p38 MAPK may attenuate ischemia-reperfusion injury. 展开更多
关键词 INTESTINES Ischemia-reperfusion injury p38 mitogen-activated protein kinase ApOpTOSIS
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Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase 被引量:8
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作者 Sergiy Kostenko Gianina Dumitriu +1 位作者 Kari Jenssen Lgreid Ugo Moens 《World Journal of Biological Chemistry》 CAS 2011年第5期73-89,共17页
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
关键词 mitogen-activated protein kinasE p38- regulated/activated protein kinasE Extracellular signalregulated kinasE protein kinasE A SUBCELLULAR localization phosphorylation protein interaction
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Mitogen activated protein kinase signaling pathways participate in the active principle region of Buyang Huanwu decoction-induced differentiation of bone marrow mesenchymal stem cells 被引量:2
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作者 Jinghui Zheng Jian Liang +6 位作者 Xin Deng Xiaofeng Chen Fasheng Wu Xiaofang Zhao Yuan Luo Lei Fu Zuling Jiang 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第18期1370-1377,共8页
Our preliminary studies confirmed that an active principle region of Buyang Huanwu decoction, comprising alkaloid, polysaccharide, aglycon, glucoside and volatile oil, can induce bone marrow mesenchymal stem cell diff... Our preliminary studies confirmed that an active principle region of Buyang Huanwu decoction, comprising alkaloid, polysaccharide, aglycon, glucoside and volatile oil, can induce bone marrow mesenchymal stem cell differentiation into neurons. Mitogen-activated protein kinase signaling was identified as one of the key pathways underlying this differentiation process. The present study shows phosphorylated extracellular signal-regulated protein kinase and phosphorylated p38 protein expression was increased after differentiation. Cellular signaling pathway blocking agents, PD98059 and SB203580, inhibited extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways respectively, mRNA and protein expression of the neuronal marker, neuron specific enolase, and neural stem cell marker, nestin, were decreased in bone marrow mesenchymal stem cells after treatment with the active principle region of Buyang Huanwu decoction. Experimental findings indicate that, extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways participate in bone marrow mesenchymal stem cell differentiation into neuron-like cells, induced by the active principle region of Buyang Huanwu decoction. 展开更多
关键词 Buyang Huanwu decoction bone marrow mesenchymal stem ceils extracellular signal-regulatedprotein kinase mitogen-activated protein kinase signaling pathway neuron specific enolase NESTIN cell signal transduction pathway neural regeneration
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Hippocampal activation of c-Jun N-terminal kinase,protein kinase B,and p38 mitogen-activated protein kinase in a chronic stress rat model of depression 被引量:1
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作者 Wei Dai Weidong Li +2 位作者 Jun Lu Yingge A Ya Tu 《Neural Regeneration Research》 SCIE CAS CSCD 2010年第19期1486-1490,共5页
Recent studies have shown that varied stress stimuli activate c-Jun N-terminal kinase (JNK), protein kinase B (Akt), and p38 mitogen-activated protein kinase (p38) signal transduction pathway, and also regulate ... Recent studies have shown that varied stress stimuli activate c-Jun N-terminal kinase (JNK), protein kinase B (Akt), and p38 mitogen-activated protein kinase (p38) signal transduction pathway, and also regulate various apoptotic cascades. JNK and p38 promote apoptosis, but Akt protects against apoptosis, in hippocampal neurons. However, changes in the transduction pathway in different regions of brain tissues in a chronic stress rat model of depression remain poorly understood. Results from this study showed that JNK phosphorylation levels were significantly greater in the stress group hippocampus compared with the control group (P 〈 0.05). No significant difference in JNK phosphorylation levels was detected in the rat cerebral cortex between stress and control groups, and no significant difference in Akt and p38 phosphorylation levels was detected in the rat hippocampus and cerebral cortex between stress and control groups (P 〉 0.05). These results suggested that the JNK signal pathway is activated by JNK phosphorylation and participates in pathophysiological changes in rat models of depression. 展开更多
关键词 DEpRESSION chronic stress pHOSpHORYLATION stress-activated protein kinase protein kinase B p38 mitogen-activated protein kinase neural regeneration
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Influence of electroacupuncture on mitogen-activated protein kinase signal transduction in a rat model of cerebral ischemia/reperfusion 被引量:1
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作者 Zhongren Li Meihong Shen +1 位作者 Wenmin Niu Xiaoren Xiang 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第30期2362-2366,共5页
Following electroacupuncture at Baihui (DU 20) and Dazhui (DU 14) in a rat model of cerebral ischemia/reperfusion, extracellular-signal-regulated kinase expression in cerebral cortex and corpus striatum, serum glu... Following electroacupuncture at Baihui (DU 20) and Dazhui (DU 14) in a rat model of cerebral ischemia/reperfusion, extracellular-signal-regulated kinase expression in cerebral cortex and corpus striatum, serum glutathione reductase, glutathione peroxidase activity, and serum glutathione content were elevated, and neurobehavioral scores improved. However, these effects were antagonized by mitogen-activated protein kinase inhibitor PD98059. Results indicated that electroacupuncture reversed free radical chain reactions and oxidative stress injury caused by cerebral ischemia/reperfusion, thereby providing neuroprotection. This process could correlate with the mitogen-activated protein kinase signal transduction pathway. 展开更多
关键词 anti-oxidative stress cerebral ischemia/reperfusion ELECTROACUpUNCTURE mitogen-activated protein kinase pathway signal transduction
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Inhibiting p38 mitogen-activated protein kinase attenuates cerebral ischemic injury in Swedish mutant amyloid precursor protein transgenic mice 被引量:1
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作者 Liangyu Zou Haiyan Qin +3 位作者 Yitao He Heming Huang Yi Lu Xiaofan Chu 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第14期1088-1094,共7页
Cerebral ischemia was induced using photothrombosis 1 hour after intraperitoneal injection of the p38 mitogen-activated protein kinase (MAPK) inhibitor $B239063 into Swedish mutant amyloid precursor protein (APP/SW... Cerebral ischemia was induced using photothrombosis 1 hour after intraperitoneal injection of the p38 mitogen-activated protein kinase (MAPK) inhibitor $B239063 into Swedish mutant amyloid precursor protein (APP/SWE) transgenic and non-transgenic mice. The number of surviving neurons in the penumbra was quantified using Nissl staining, and the activity of p38 MAPKs was measured by western blotting. The number of surviving neurons in the penumbra was significantly reduced in APP/SWE transgenic mice compared with non-transgenic controls 7 days after cerebral ischemia, but the activity of p38 MAPKs was significantly elevated compared with the non-ischemic hemisphere in the APP/SWE transgenic mice. SB239063 prevented these changes. The APP/SWE mutation exacerbated ischemic brain injury, and this could be alleviated by inhibiting p38 MAPK activity. 展开更多
关键词 cerebral ischemia amyloid precursor protein TRANSGENIC Alzheimer's disease p38mitogen-activated protein kinase SB239063 neural regeneration
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INVOLVEMENT OF p38 MITOGEN-ACTIVATED PROTEIN KINASE IN E.coli-INDUCED U937 APOPTOSIS 被引量:1
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作者 Jia-he Wang Yi-jun Zhou +1 位作者 Ping He Bai-yi Chen 《Chinese Medical Sciences Journal》 CAS CSCD 2007年第1期49-53,共5页
Objective To investigate whether the effect of E. coli on U937 cell fines apoptosis is mediated via p38 mitogen-activated protein kinase (MAPK) activation. Methods The U937 cell lines were treated with E. coli at d... Objective To investigate whether the effect of E. coli on U937 cell fines apoptosis is mediated via p38 mitogen-activated protein kinase (MAPK) activation. Methods The U937 cell lines were treated with E. coli at different time or together with SB203580, an inhibitor for p38. Cell apoptosis was analyzed by flow cytometry, p38 activities were detected by Western blotting. Results E. coli induced apoptosis in cultured U937 cell lines in a time-dependent manner. The phosphorylation of p38 was induced after 10 minutes infection, reached the peak after 20 minutes, and started to decline after 30 minutes. In contrast, the level of total p38 protein was not changed in whole experimental period. Inhibition of p38 with SB203580 significantly inhibited E. coli induced apoptosis in U937 cells. Conclusion The activation of the p38 MAPK in U937 cell lines by E. coli is a major pathway to mediate the apoptosis. 展开更多
关键词 E. coli ApOpTOSIS U937 p38 mitogen-activated protein kinase
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p38 mitogen-activated protein kinase regulates type-Ⅰ vs type-Ⅱ phenotyping of human vascular endothelial cells 被引量:1
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作者 Masako Nakahara Miwako Nishio +2 位作者 Koichi Saeki Akira Yuo Kumiko Saeki 《World Journal of Translational Medicine》 2015年第3期101-112,共12页
AIM: To identify kinases involved in phenotype regulation of vascular endothelial cells(VECs): Proproliferative G-protein signaling 5(RGS5)^(high)(typeⅠ) vs anti-proliferative RGS5^(low)(typeⅡ) VECs.METHODS: Proteom... AIM: To identify kinases involved in phenotype regulation of vascular endothelial cells(VECs): Proproliferative G-protein signaling 5(RGS5)^(high)(typeⅠ) vs anti-proliferative RGS5^(low)(typeⅡ) VECs.METHODS: Proteomic kinase assays were performed to identify the crucial kinase involved in the phenotype regulation of human VECs using typeⅠ VECs, which promotes the proliferation of human vascular smooth muscle cells(VSMCs), and typeⅡ VECs, which suppress the proliferation of human VSMCs. The assays were performed using multiple pairs of typeⅠ and typeⅡ VECs to obtain the least number of candidates. The involvement of the candidate kinases was verified by evaluating the effects of their specific inhibitors on the phenotype regulation of human VECs as well as the expression levels of regulator of RGS5, which is the causative gene for the "typeⅡ to typeⅠ" phenotype conversion of human VECs. RESULTS: p38α mitogen-activated protein kinase(p38α MAPK) was the only kinase that showed distinctive activities between typeⅠ and typeⅡ VECs: p38α MAPK activities were low and high in type-Ⅰand typeⅡ VECs, respectively. We found that an enforced expression of RGS5 indeed lowered p38α MAPK activitiesin typeⅡ VECs. Furthermore, treatments with a p38α MAPK inhibitor nullified the anti-proliferative potential in typeⅡ VECs. Interestingly, MAPK inhibitor treatments enhanced the induction of RGS5 gene. Thus, there is a vicious cycle between "RGS5 induction" and "p38α MAPK inhibition", which can explain the unidirectional process in the stress-induced "typeⅡ to typeⅠ" conversions of human VECs. To understand the upstream signaling of RGS5, which is known as an inhibitory molecule against the G protein-coupled receptor(GPCR)-mediated signaling, we examined the effects of RGS5 overexpression on the signaling events from sphingosine-1-phosphate(S1P) to N-cadherin, because S1 P receptors belong to the GPCR family gene and N-cadherin, one of their downstream effectors, is reportedly involved in the regulation of VEC-VSMC interactions. We found that RGS5 specifically bound with S1P1. Moreover, N-cadherin localization at intercellular junctions in typeⅡ VECs was abolished by "RGS5 overexpression" and "p38α MAPK inhibition".CONCLUSION: p38α MAPK plays crucial roles in "type-Ⅰ vs type-Ⅱ" phenotype regulations of human VECs at the downstream of RGS5. 展开更多
关键词 VASCULAR endothelial CELLS VASCULAR smooth muscle CELLS proteomic kinasE assay p38αmitogenactivated protein kinasE regulator of G-protein signaling 5 sphingosine-1-phosphate N-cadherin
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Role of p38 Mitogen-activated Protein Kinase in Mediating Monocyte Chemoattractant Protein-1 in Human Umbilical Vein Endothelial Cells
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作者 李艳波 邓华聪 +1 位作者 郑丹 李呼伦 《Chinese Medical Sciences Journal》 CAS CSCD 2004年第1期71-71,共1页
关键词 Cells Cultured Endothelial Cells Humans mitogen-activated protein kinases Monocyte Chemoattractant protein-1 RNA Messenger Research Support Non-U.S. Gov't Umbilical Veins p38 mitogen-activated protein kinases
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Functional study of p38 mitogen-activated protein kinase based on cell-penetrating peptide delivery system
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作者 Liping Yang Yongming Yao Zhiyong Sheng Xiaomei Zhu Yong Jiang 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2009年第2期108-114,共7页
Objective p38 Mitogen-activated protein kinase (MAPK) is a crossing center of various pathways. In this study, protein transduction system based on human immunodeficiency virus (HIV)-1 transactivator of transcript... Objective p38 Mitogen-activated protein kinase (MAPK) is a crossing center of various pathways. In this study, protein transduction system based on human immunodeficiency virus (HIV)-1 transactivator of transcription (TAT), which is an efficient delivery peptide of the foreign proteins into cells, was employed to study p38 MAPK functions in eukaryotic cells. Methods p38 And its dominant negative form, p38AF, were constructed into pET-His-TAT vector correctly to verify that the recombinant plasmids were well-founded through restriction enzyme digestion and DNA sequencing. The two proteins, His-TAT-p38 and His-TAT-p38AF, were expressed and purified in Escherichia coli by SDS-PAGE. Then they were incubated with ECV304 cells respectively and readily transduced into cells in a time-dependent and dose-dependent manner. The cells were stimulated by sorbitol. Activating transcription factor (ATF) 2 phosphorylation level was checked using Western blot to assess the activity of endogenous p38. Results Compared with controls, it was found that His-TAT-p38 increased the level ofATF2 phosphorylation in sorbitol-stimulated ECV304 cells, while His-TAT-p38AF inhibited it, indicating p38 MAPK protein delivery system based on TAT was constructed successfully. TAT-p38 and its dominant negative form possessed high biological activity after transduction into ECV304 cells by TAT protein delivery system. The results showed that p38AF fused with TAT could inhibit the transduction of endogenous p38 signal pathway in part, and other pathway might regulate p38 phosphorylation. Conclusions Our study provides a novel pathway to inhibit p38 signal pathway and establish a new method to study p38 function. 展开更多
关键词 Human immunodeficiency virus-1 transactivator of transcription p38 mitogen-activated protein kinase protein transduction: sorbitol
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Neuroprotective mechanisms of rutin for spinal cord injury through anti-oxidation and anti-inflammation and inhibition of p38 mitogen activated protein kinase pathway 被引量:10
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作者 Hong-liang Song Xiang Zhang +5 位作者 Wen-zhao Wang Rong-han Liu Kai Zhao Ming-yuan Liu Wei-ming Gong Bin Ning 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第1期128-134,共7页
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
关键词 nerve regeneration spinal cord injury RUTIN oxidative stress antioxidant ANTI-INFLAMMATION p38 mitogen activated protein kinase pathway ANTI-ApOpTOSIS caspase-3 caspase-9 neural regeneration
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Mitogen-activated protein kinase phosphatase 1 protects PC12 cells from amyloid beta-induced neurotoxicity 被引量:6
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作者 Yue Gu Lian-Jun Ma +4 位作者 Xiao-Xue Bai Jing Jie Xiu-Fang Zhang Dong Chen Xiao-Ping Li 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第10期1842-1850,共9页
The mitogen-activated protein kinase(MAPK) signaling pathway plays an important role in the regulation of cell growth, proliferation, differentiation, transformation and death. Mitogen-activated protein kinase phosp... The mitogen-activated protein kinase(MAPK) signaling pathway plays an important role in the regulation of cell growth, proliferation, differentiation, transformation and death. Mitogen-activated protein kinase phosphatase 1(MKP1) has an inhibitory effect on the p38 MAPK and JNK pathways, but it is unknown whether it plays a role in Aβ-induced oxidative stress and neuronal inflammation. In this study, PC12 cells were infected with MKP1 sh RNA, MKP1 lentivirus or control lentivirus for 12 hours, and then treated with 0.1, 1, 10 or 100 μM amyloid beta 42(Aβ42). The cell survival rate was measured using the cell counting kit-8 assay. MKP1, tumor necrosis factor-alpha(TNF-α) and interleukin-1β(IL-1β) m RNA expression levels were analyzed using quantitative real time-polymerase chain reaction. MKP1 and phospho-c-Jun N-terminal kinase(JNK) expression levels were assessed using western blot assay. Reactive oxygen species(ROS) levels were detected using 2′,7′-dichlorofluorescein diacetate. Mitochondrial membrane potential was measured using flow cytometry. Superoxide dismutase activity and malondialdehyde levels were evaluated using the colorimetric method. Lactate dehydrogenase activity was measured using a microplate reader. Caspase-3 expression levels were assessed by enzyme-linked immunosorbent assay. Apoptosis was evaluated using the terminal deoxynucleotidyl transferase d UTP nick end labeling method. MKP1 overexpression inhibited Aβ-induced JNK phosphorylation and the increase in ROS levels. It also suppressed the Aβ-induced increase in TNF-α and IL-1β levels as well as apoptosis in PC12 cells. In contrast, MKP1 knockdown by RNA interference aggravated Aβ-induced oxidative stress, inflammation and cell damage in PC12 cells. Furthermore, the JNK-specific inhibitor SP600125 abolished this effect of MKP1 knockdown on Aβ-induced neurotoxicity. Collectively, these results show that MKP1 mitigates Aβ-induced apoptosis, oxidative stress and neuroinflammation by inhibiting the JNK signaling pathway, thereby playing a neuroprotective role. 展开更多
关键词 nerve regeneration mitogen-activated protein kinase phosphatase 1 c-Jun N-terminal kinase signaling pathway Alzheimer's disease neurons DEMENTIA apoptosis RNA interference lentivirus inflammation oxidative stress neural regeneration
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Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infection 被引量:3
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作者 Jia You Jing Lin +6 位作者 Yi-Fan Zhou Xu-Dong Peng Hong He Cui Li Guo-Qiang Zhu Xue-Qi Zhao Gui-Qiu Zhao 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2019年第4期549-556,共8页
AIM: To investigate the expression of interleukin(IL)-33 in the cornea and human corneal epithelial cells(HCECs) exposed to Aspergillus fumigatus(A. fumigatus), and to determine the function of IL-33/ST2/p38 signaling... AIM: To investigate the expression of interleukin(IL)-33 in the cornea and human corneal epithelial cells(HCECs) exposed to Aspergillus fumigatus(A. fumigatus), and to determine the function of IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to A. fumigatus infection.METHODS: The mRNA and protein expression of IL-33 in HCECs and mice corneas were examined by quantitative real-time reverse transcription polymerase chain reaction(q RT-PCR) and Western blot analysis, respectively. IL-33 expression was also detected in cornea samples from healthy donors and patients with fungal keratitis with immunohistochemistry. The cultured HCECs were treated with inactive A. fumigatus hyphae at various concentrations with or without recombinant human IL-33 protein, soluble recombinant ST2 protein, specific ST2 neutralizing antibody, or the mitogen-activated protein kinase(MAPK) p38 inhibitor SB203580 for evaluation of the expression and activation of IL-33/ST2/p38 signaling in the regulation of proinflammatory cytokines. The production levels of IL-6 and IL-1β were determined by qR T-PCR and enzymelinked immunosorbent assay(ELISA). The proliferation of HCECs was determined by a Cell Counting Kit-8(CCK8) assay and cell count.RESULTS: IL-33 expression levels increased in the corneal tissues of patients with fungal keratitis and in mice corneas of experimental A. fumigatus infection,as well as in HCECs with infection of A. fumigatus. A. fumigatus strongly stimulated HCECs-generated proinflammatory cytokine(IL-6 and IL-1β) production at both the mRNA and protein levels. This production of proinflammatory mediators stimulated by A. fumigatus was further stimulated by IL-33 and was prevented by soluble ST2 protein or ST2 neutralizing antibody. Moreover, IL-33 naturally promoted the p38 phosphorylation induced by A. fumigatus, which was suppressed by soluble ST2 protein. The MAPK p38 inhibitor SB203580 also inhibited the A. fumigatus-induced proinflammatory cytokine production. IL-33 administration for 48 h and 72 h promoted the proliferation of HCECs, which was attenuated by treatment with soluble recombinant human ST2 protein.CONCLUSION: A. fumigatus elevates IL-33 expression in human and mice corneas and HCECs. Thus, IL-33/ST2/p38 signaling may play an important role in amplifying the immune response of corneal epithelial cells to A. fumigatus infection. Besides, IL-33 promotes the cell proliferation of HCECs via its receptor ST2. These findings suggest a novel autocrine mechanism of amplification of the fungalinduced inflammatory response in the corneal epithelium, highlighting a potential therapeutic target for fungal keratitis. 展开更多
关键词 ST2 INTERLEUKIN 33 Aspergillus FUMIGATUS CORNEA p38 mitogen-activated protein kinase proliferation
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Interleukin-1 beta up-regulates tissue inhibitor of matrix metalloproteinase-1 mRNA and phosphorylation of c-jun N-terminal kinase and p38 in hepatic stellate cells 被引量:22
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作者 Ya-Ping Zhang Xi-Xian Yao Xia Zhao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第9期1392-1396,共5页
AIM: To study the relationship between interleukin-lbeta (IL-1β) up-regulating tissue inhibitor of matrix metalloproteinase-1 (TIMMP-1) mRNA expression and phosphorylation of both c-jun N-terminal kinase (INK)... AIM: To study the relationship between interleukin-lbeta (IL-1β) up-regulating tissue inhibitor of matrix metalloproteinase-1 (TIMMP-1) mRNA expression and phosphorylation of both c-jun N-terminal kinase (INK) and p38 in rat heffatic stellate cells (HSC). METHODS: RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC. RESULTS: TIMMP-1 mRNA expression (1.191± 0.079) was much higher after treatment with IL-1β (10 ng/mL) for 24 h than in control group (0.545±0.091) (P〈0.01). IL-1β activated INK and p38 in a time-dependent manner. After stimulation with IL-1β for 0, 5, 15, 30, 60 and 120 min, the INK activity was 0.982±0.299, 1.501±0.720, 2.133±0.882, 3.360±0.452, 2.181±0.789, and 1.385 ± 0.368, respectively. There was a significant difference in JNK activity at 15 min (P〈 0.01), 30 min (P〈 0.01) and 60 min (P〈0.01) in comparison to that at 0 min. The p38 activity was 1.061±0.310, 2.050±0.863, 2.380±0.573, 2.973±0.953, 2.421±0.793, and 1.755 ± 0.433 at the 6 time points (0, 5, 15, 30, 60 and 120 min) respectively. There was a significant difference in p38 activity at 5 min (P〈0.05), 15 min (P〈0.01), 30 min (P〈0.01) and 60 min (P〈0.01) compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups pretreated with different concentrations of SP600125 (10 μmol/L, 1.022±0.113; 20 μmol/L, 0.869±0.070; 40 μmol/L, 0.666±0.123). Their decreases were all significant (P〈0.05, P〈0.01, P〈0.01) in comparison to control group (without SP600125 treatment, 1.163±0.107). In the other 3 groups pretreated with different concentrations of SB203580 (10 μmol/L, 1.507±0.099; 20 μmol/L, 1.698±0.107; 40 μmol/L, 1.857±0.054), the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group (without SB203580 treatment, 1.027 ± 0.061) with a significant statistical significance (P〈 0.01). CONCLUSION: IL-1β has a direct action on hepatic fibrosis by up-regulating TIMMP-1 mRNA expression in ratessionin in rate HSC.JNK and p38 mitogen-activated protein kinases (MAPKs) are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and .INK pathways cooperatively mediate TIMP-1 mRNA expression in rat HSC. 展开更多
关键词 Up-Regulation Animals ANTHRACENES Blotting Western Cell Line Enzyme Inhibitors IMIDAZOLES INTERLEUKIN-1 JNK mitogen-activated protein kinases Liver Liver Cirrhosis pHOSpHORYLATION pYRIDINES RNA Messenger Rats Reverse Transcriptase polymerase Chain Reaction signal Transduction Time Factors Tissue Inhibitor of Metalloproteinase-1 p38 mitogen-activated protein kinases
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Inflammation-and stress-related signaling pathways in hepatocarcinogenesis 被引量:19
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作者 Hayato Nakagawa Shin Maeda 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第31期4071-4081,共11页
It has been established that cancer can be promoted and exacerbated by inflammation.Hepatocellular carcinoma(HCC) is the fifth most common cancer worldwide,and its long-term prognosis remains poor.Although HCC is a co... It has been established that cancer can be promoted and exacerbated by inflammation.Hepatocellular carcinoma(HCC) is the fifth most common cancer worldwide,and its long-term prognosis remains poor.Although HCC is a complex and heterogeneous tumor with several genomic mutations,it usually develops in the context of chronic liver damage and inflammation,suggesting that understanding the mechanism(s) of inflammation-mediated hepatocarcinogenesis is essential for the treatment and prevention of HCC.Chronic liver damage induces a persistent cycle of necroinflammation and hepatocyte regeneration,resulting in genetic mutations in hepatocytes and expansion of initiated cells,eventually leading to HCC development.Recently,several inflammation-and stress-related signaling pathways have been identified as key players in these processes,which include the nuclear factor B,signal transducer and activator of transcription,and stress-activated mitogen-activated protein kinase pathways.Although these pathways may suggest potential therapeutic targets,they have a wide range of functions and complex crosstalk occurs among them.This review focuses on recent advances in our understanding of the roles of these signaling pathways in hepatocarcinogenesis. 展开更多
关键词 Hepatocellular carcinoma INFLAMMATION Nuclear factor-~B mitogen-activated protein kinase signal transducer and activator of transcription c-JunNH2-terminal kinase p38 Transforming growth factor-activated kinase 1 Apoptosis signal-regulating kinase 1
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PBX3 promotes migration and invasion of colorectal cancer cells via activation of MAPK/ERK signaling pathway 被引量:12
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作者 Hai-Bo Han Jin Gu +5 位作者 Deng-Bo Ji Zhao-Wei Li Yuan Zhang Wei Zhao Li-Min Wang Zhi-Qian Zhang 《World Journal of Gastroenterology》 SCIE CAS 2014年第48期18260-18270,共11页
AIM: To investigate the role of pre-B-cell leukemia homeobox (PBX)3 in migration and invasion of colorectal cancer (CRC) cells.
关键词 pre-B-cell leukemia homeobox 3 Colorectal cancer Cell migration Cell invasion mitogen-activated protein kinase signaling pathway
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Down-regulation of HIV-1 Infection by Inhibition of the MAPK Signaling Pathway 被引量:3
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作者 Jian Gong Xi-hui Shen +2 位作者 Chao Chen Hui Qiu Rong-ge Yang 《Virologica Sinica》 SCIE CAS CSCD 2011年第2期114-122,共9页
The human immunodeficiency virus type 1 (HIV-1) can interact with and exploit the host cellular machinery to replicate and propagate itself. Numerous studies have shown that the Mitogen-activated protein kinase (M... The human immunodeficiency virus type 1 (HIV-1) can interact with and exploit the host cellular machinery to replicate and propagate itself. Numerous studies have shown that the Mitogen-activated protein kinase (MAPK) signal pathway can positively regulate the replication of HIV-1, but exactly how each MAPK pathway affects HIV-1 infection and replication is not understood. In this study, we used the Extracellular signal-regulated kinase (ERK) pathway inhibitor, PD98059, the Jun N-terminal kinase (JNK) pathway inhibitor, SP600125, and the p38 pathway inhibitor, SB203580, to investigate the roles of these pathways in HIV-1 replication. We found that application of PD98059 results in a strong VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus and HIV-1NL4-3 virus inhibition activity. In addition, SB203580 and SP600125 also elicited marked VSV-G pseudotyped HIV-INL4-3 luciferase reporter virus inhibition activity but no HIV-1NL4-3 virus inhibition activity. We also found that SB203580 and SP600125 can enhance the HIV-1 inhibition activity of PD98059 when cells were treated with all three MAPK pathway inhibitors in combination. Finally, we show that HIV-1 virus inhibition activity of the MAPK pathway inhibitors was the result of the negative regulation of HIV-1 LTR promoter activity. 展开更多
关键词 HIV-1 inhibition mitogen-activated protein kinase (MApK) Extracellular signal-regulated kinase (ERK) Jun N-terminal kinase (JNK) p38 LTR activation
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IL-1RⅠ/MyD88-TIR mimic AS-1 inhibits the activation of MyD88-dependent signaling pathway induced by IL-1β in vitro 被引量:2
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作者 Yulong Hu Ting Li Yong mei Wang Lin Guo Xiaohong Shan Jing Li Qi Chen Yuehua Li 《Journal of Nanjing Medical University》 2007年第6期354-358,共5页
Objective: To test whether IL-1 RI/My088-TIR mimic AS-1 can work as a new compound that targeted at blocking MyD88- dependent signaling pathway, we investigated the physical structure and biological function of AS-1.... Objective: To test whether IL-1 RI/My088-TIR mimic AS-1 can work as a new compound that targeted at blocking MyD88- dependent signaling pathway, we investigated the physical structure and biological function of AS-1. Methods:The crystallographic structure of AS-1 was examined by 1^H nuclear magnetic resonance. The toxicity of AS-1 was measured with Methyl thiazolyl tetrazolium (MTT) assay. The effect of AS-1 on phosphorylation state of p38 MAPK and IRAK-1 was observed with Western blot. Results:The crystallographic details of AS-1 demonstrated that it was a tri-peptide sequence[(F/Y)-(V/L/I)-(P/G)] of the IL-1R I -TIR domain BBloop. No toxicity of AS-1 was shown to HEK 293A cells. The phosphorylation of p38 MAPK, induced by IL-1β significantly increased from those in the control group. AS-1 significantly reduced the phosphorylation of p38 MAPK induced by IL-1β. IL-1β increased the phosphorylation of IRAK-1 significantly, which was prevented by AS-1. Conclusion:AS-1 is a competitive mimic between IL-1R I-TIR and MyD88-TIR domain, which most likely interferes with MyD88-dependent signaling pathway. 展开更多
关键词 hydrocinnamoyl-L-valyl pyrrolidine(AS-1) MYD88 IRAK-1 mitogen-activated protein kinases signaling pathway
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