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The roles of the proteasome pathway in signal transduction and neurodegenerative diseases 被引量:2
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作者 陈皎皎 林芳 秦正红 《Neuroscience Bulletin》 SCIE CAS CSCD 2008年第3期183-194,共12页
There are two degradation systems in mammalian cells, autophagy/lysosomal pathway and ubiquitin-proteasome pathway. Proteasome is consist of multiple protein subunits and plays important roles in degradation of short-... There are two degradation systems in mammalian cells, autophagy/lysosomal pathway and ubiquitin-proteasome pathway. Proteasome is consist of multiple protein subunits and plays important roles in degradation of short-lived cellular proteins. Recent studies reveal that proteasomal degradation system is also involved in signal transduction and regulation of various cellular functions. Dysfunction or dysregulation of proteasomal function may thus be an important pathogenic mechanism in certain neurological disorders. This paper reviews the biological functions of proteasome in signal transduction and its potential roles in neurodegenerative diseases. 展开更多
关键词 PROTEASOME signal transduction protein misfolding neurodegenerative disease
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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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Acupuncture activates signal transduction pathways related to brain-tissue restoration after ischemic injury 被引量:9
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作者 Haomei Tian Hong Zhang +4 位作者 Junbao Zhu Juan Zhang Hening Cai Yuchen Zhang Chutao Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第24期1866-1872,共7页
A middle cerebral artery occlusion-model was established in rats using the improved thread embolism method.Rats were treated with acupuncture at either Dazhui(DU14),Renzhong(DU26), Baihui(DU20),or a non-meridian... A middle cerebral artery occlusion-model was established in rats using the improved thread embolism method.Rats were treated with acupuncture at either Dazhui(DU14),Renzhong(DU26), Baihui(DU20),or a non-meridian point.Detection with protein-chip technology showed that the level of protein phosphorylation in both groups was upregulated or downregulated depending on the signaling pathway compared with the model group that did not receive acupuncture.Analysis of proteins showing downregulated phosphorylation revealed that five signaling pathways were activated in the acupuncture-treatment group,while only two were activated in the acupuncture-control group.In contrast,analysis of proteins showing upregulated phosphorylation revealed only one pathway was activated in the acupuncture-treatment group,whereas four pathways were activated in the acupuncture-control group.Furthermore,the number of activated proteins in the acupuncture-treatment group was not only higher than the acupuncture-control group,but unlike the acupuncture-control group,the majority of activated proteins were key proteins in the signaling pathways.Our findings indicate that acupuncture at specific points can activate multiple signaling pathways to promote the restoration of brain tissue following ischemic injury,and that this is based on a combination of effects resulting from multiple pathways,targets,and means. 展开更多
关键词 ACUPUNCTURE cerebral ischemia DAZHUI Baihui RENZHONG protein-chip technology signal-transduction pathways nerve injury brain injury ischemic injury neural regeneration
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Role of myeloid differentiation factor 88 in HSP60 signal transduction in dendritic cells
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作者 Jiajun Chen Zongquan Sun Gang Su Chao Liu Jinping Liu Yongzhi Deng Jiawei Shi 《Journal of Nanjing Medical University》 2007年第1期36-41,共6页
To explore the role and mechanism of myeloid differentiation factor88 (MyD88) in HSP60 signal transduction in dendritic cells. Methods:Mouse DCs were cultured from murine bone marrow cells. The DC marker CDllc was ... To explore the role and mechanism of myeloid differentiation factor88 (MyD88) in HSP60 signal transduction in dendritic cells. Methods:Mouse DCs were cultured from murine bone marrow cells. The DC marker CDllc was detected by flow cytometry, then DCs were divided into control group, HSP60 groupand RNA interference group. Control group was cultured under normal condition, and HSP60 group was cultured with 10 μg/ml of HSP60. RNA interference group was first cultured with MyD88 siRNA for12 hours and then HSP60 was added into the culture mixture. All groups were cultured for 48 hours. Immunochemistry was used to detect the concentration of MyD88 and NF- κB. Western blot was used to detect the concentration of MyD88. Flow cytometry and mixed lymphocyte reaction (MLR) were used to detect the phenotype and functional properties of DCs. ELISA was used to detect the concentration of TNF-α, IFN-γ and IL-12 in the supernatant. Results:The expression of CDllc in murine bone marrow DCs was 88.76%. HSP60 stimulation increased the expression of CD80, CD86, MHC-Ⅱ in DCs and TNF-α, IFN-7, IL-12 secretion in the supernatant. HSP60 stimulation also increased the level of MyD88 in the cytoplasm and promoted the shift of NF-κB to karyon and the proliferation of allogeneic T cells. MyD88 siRNA could decreaseMyD88 and inhibit these effects induced by HSP60. Conclusion:HSP60 activates DCs through MyD88-dependent pathway. MyD88 plays a critical role in HSP60 signal transduction. Inhibition of MyD88 may be a novel way for treating disease correlated with HSP60. 展开更多
关键词 dendritic cells MYD88 heat-shock proteins signal transduction
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Gene Expression Modulation of Two Biosynthesis Pathways via Signal Transduction in <i>Cochliobolus heterostrophus</i>
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作者 Ofir Degani 《Advances in Bioscience and Biotechnology》 2014年第4期340-352,共13页
G-protein-linked pathways have evolved to allow responses to extracellular agonists (hormones, neurotransmitters, odors, chemoattractants, light and nutrients) in eukaryotic cells, ranging from simpler systems, includ... G-protein-linked pathways have evolved to allow responses to extracellular agonists (hormones, neurotransmitters, odors, chemoattractants, light and nutrients) in eukaryotic cells, ranging from simpler systems, including yeasts, filamentous fungi and slime molds, to more complex organisms, such as mammals. Although the role of G-protein and mitogen-activated protein kinase (MAPK) in filamentous fungi has been studied for over a decade, downstream elements are less known, and the study of target genes has evolved mainly in recent years. Here, we examined the involvement of G-protein subunits and MAPK in controlling the expression of two distinct target genes. These genes were selected from an array database according to their unique expression profile and the role of closely related genes found in other Ascomycetes. One of these genes is BPH, which encodes the enzyme responsible for cytochrome P450-dependent benzoate hydroxylation in microsomes. The other gene is CIPA, which encodes isoflavone reductase (IfR), an enzyme involved in the synthesis of phytoalexin, which catalyzes an intermediate step in pisatin biosynthesis. The expression profile of these two genes was determined in a series of signaling deficiency mutants that were grown on different media using a DNA microarray. Comparison of the expression profile in the two wild type strains and mutants deficient in the G-protein α or β subunits or in MAPK, revealed a unique control mechanism for the BPH and CIPA genes. The two genes are highly expressed during the infection of the host plant leaves and may associate with the fungal response to the host. Signaling via G-protein or MAPK was shown to be related to cascades that altered the expression of these genes in response to the growth condition. This work demonstrates that signal transduction pathways are controlling genes that, although sharing an environmental dependent response, participate in distinct biosynthesis pathways. Moreover, the transcriptional profile may point to distinct and shared roles of the signaling components. 展开更多
关键词 COCHLIOBOLUS heterostrophus Cytochrome P450-Dependent BENZOATE HYDROXYLASE G-PROTEIN Isoflavone Reductase Maize MAPK signal transduction
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Regulation of apoptotic signal transduction pathways by the heat shock proteins 被引量:8
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作者 LI Zhengyu1, ZHAO Xia1 & WEI Yuquan2 1. Department of Gynecology and Obstetrics, West China Second Hospital of Sichuan University, Chengdu 610041, China 2. Key Laboratory of Biotherapy of Human Diseases of Ministry of Education, West China Hospital of Sichuan university, Chengdu 610041, China 《Science China(Life Sciences)》 SCIE CAS 2004年第2期107-114,共8页
The study about apoptotic signal transductions has become a project to reveal the molecular mechanisms of apoptosis. Heat shock proteins (hsps), which play an important role in cell growth and apoptosis, have attracte... The study about apoptotic signal transductions has become a project to reveal the molecular mechanisms of apoptosis. Heat shock proteins (hsps), which play an important role in cell growth and apoptosis, have attracted great attentions. A lot of researches have showed there is a hsps superfamily including hsp90, hsp70, hsp60 and hsp27, etc., which regulates the bio-logical behaviors of cells, particularly apoptotic signal transduction in Fas pathway, JNK/SAPK pathway and caspases pathway at different levels, partly by the function of molecular chaperone. 展开更多
关键词 heat shock protein APOPTOTIC signal transduction MOLECULAR chaperone caspases.
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Gibberellin Signal Transduction in Rice 被引量:12
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作者 Liu-Min Fan Xiaoyan Feng +1 位作者 Yu Wang Xing Wang Deng 《Journal of Integrative Plant Biology》 SCIE CAS CSCD 2007年第6期731-741,共11页
In the past decade, significant knowledge has accumulated regarding gibberellin (GA) signal transductlon In rice as a result of studies using multiple approaches, particularly molecular genetics. The present review ... In the past decade, significant knowledge has accumulated regarding gibberellin (GA) signal transductlon In rice as a result of studies using multiple approaches, particularly molecular genetics. The present review highlights the recent developments In the identification of GA signaling pathway components, the discovery of GA-Induced destructlon of GA signaling repressor (DELLA protein), and the possible mechanism underlying the regulation of GA- responsive gene expression in rice. 展开更多
关键词 gene expression GIBBERELLIN protein degradation RICE signal transduction.
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Small G Protein as a Novel Component of the Rice Bmssinosteroid Signal Transduction 被引量:6
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作者 Ge Zhang Xiaoguang Song +3 位作者 Hongyan Guo Yao Wu Xiaoying Chen Rongxiang Fang 《Molecular Plant》 SCIE CAS CSCD 2016年第9期1260-1271,共12页
Brassinosteroids (BRs) are a class of steroid hormones that are essential for plant growth and development. The BR signal transduction pathway in the dicot model plantArabidopsis is well established, but the compone... Brassinosteroids (BRs) are a class of steroid hormones that are essential for plant growth and development. The BR signal transduction pathway in the dicot model plantArabidopsis is well established, but the components connecting the BR signaling steps in rice have not been fully explored. For example, how the BR signaling is fine-tuned in rice, especially at the BR receptor level, is largely unknown. Here we show that OsPRA2, a rice small G protein, plays a repressive role in the BR signaling pathway. Lamina inclination, coleoptile elongation, and root inhibition assays indicated that rice plants with suppressed expression of OsPRA2 were more sensitive to exogenously applied brassinolide than the wild-type plants. Conversety, rice overexpressing OsPRA2 was less sensitive to exogenous brassinolide. Further study uncovered that OsPRA2 inhibited the dephosphorylation of, and thus inactivated the transcription factor BRASSINAZOLE- RESISTANT 1 (OsBZR1). More importantly, OsPRA2 was found to co-localize with and directly bind to rice BR receptor BRASSlNOSTEROID-INSENSITIVE 1 (OsBRI1) at the plasma membrane. Additionally, the in vitro assays showed that OsPRA2 inhibits its autophosphorylation. This OsPRA2-OsBRI1 interaction led to the dissociation of OsBRI1 from its co-receptor OsBAK1, and abolished OsBRIl-mediated phosphorylation of OsBAK1. Together, these results reveal a possible working mechanism of OsPRA2 as a novel negative regu- lator on OsBRI1 and OsBZR1 and extend the knowledge about the regulatory mechanism of rice BR signaling. 展开更多
关键词 BRASSINOSTEROID small G protein plant hormone signal transduction
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Effect of cigarette smoke extract on lipopolysaccharide-activated mitogen-activated protein kinase signal transduction pathway in cultured cells 被引量:3
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作者 LI Wen XU Yong-jian SHEN Hua-hao 《Chinese Medical Journal》 SCIE CAS CSCD 2007年第12期1075-1081,共7页
Background Lipopolysaccharide (LPS) forms outer membrane of the wall of Gram-negative cells. LPS can directly cause damage to epithelia of respiratory tract and is the major factor responsible for the chronic inflam... Background Lipopolysaccharide (LPS) forms outer membrane of the wall of Gram-negative cells. LPS can directly cause damage to epithelia of respiratory tract and is the major factor responsible for the chronic inflammation of respiratory passage. The mitogen-activated protein kinase (MAPK) signal transduction pathway of the airway epithelia is intimately associated with the action of LPS. The chronic inflammation of respiratory tract and smoking are interrelated and entwined in the development and progression of chronic lung diseases. This study was designed to examine the effects of cigarette smoke extract (CSE) and LPS on MAPK signal transduction pathway in order to further understand the roles CSE and LPS play in chronic lung inflammation. Methods Cultured primary human epithelial cells of airway were divided into four groups according to the stimulants used: blank control group, LPS-stimulation group, CSE-stimulation group and CSE plus LPS group. Western blotting was employed for the detection of phosphorylation level of extracellular-signal-regulated-kinase (ERK1/2), p38 MAPK and c-Jun N-terminal kinase (JNK). The expression of cytokines of MAPK transduction pathway (granulocyte-macrophage colony stimulating factor (GM-CSF) and mRNA of IL-8) in the primary epithelial cells of respiratory tract was also determined. Results Western blotting revealed that the phosphorylation levels of ERK1/2, p38 MAPK and JNK were low and 2 hours after the LPS stimulation, the phosphorylation of ERK1/2, p38 MAPK and JNK were all increased. There was a significant difference in the phosphorylation between the LPS-stimulation group and blank control group (P〈0.05); no significant difference was found between CSE-stimulation group and blank control group (P〉0.05); there was a significant difference between CSE + LPS group and blank control group and between CSE + LPS group and LPS group (P〈0.05). The phosphorylation of CSE-LPS group was higher than that of blank control group but lower than that of LPS group. In blank control group, the expression of IL-8 and GM-CSF mRNA was low in the epithelial cells of airway and the release of IL-8 and GM-CSF was also at a low level. One hour after LPS stimulation, the level of IL-8 mRNA increased (P〈0.05) and reached a peak after 2 hours. On the other hand, GM-CSF mRNA level increased 2 hours after the stimulation (P〈0.05) and reached the highest level 4 hours after the stimulation. Two hours after LPS stimulation, IL-8 and GM-CSF protein level began to rise (P〈0.05), and the level was the highest 8 hours after the stimulation (P〈0.01). Stimulation with CSE alone had no effect on the release of IL-8 and GM-CSF and expression of IL-8 mRNA (P〉0.05), but pre-treatment with CSE could delay the LPS-induced release of IL-8 and GM-CSF and the expression of IL-8 mRNA and its peak was lower. Conclusions LPS stimulation can significantly increase the phosphorylation of ERK1/2, p38 MAPK and JNK in the epithelial cells of airway and activate the MAPK transduction pathway, thereby can activate the downstream signal transduction pathway, and can ultimately result in the release of cytokines by the epithelial cells of airway. CSE can partially abolish the LPS-induced activation of MAPK signal transduction pathway and the expression of cytokines of the pathway, which might contribute to the development and progression of the inflammatory reactions in COPD patients. 展开更多
关键词 SMOKING LIPOPOLYSACCHARIDE mitogen-activated protein kinase signal transduction pathway INTERLEUKIN-8 epithelial cells granulocyte-macrophage colony stimulating factor
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Effect of proline rich domain of an RNA-binding protein Sam68 in cell growth process, death and B cell signal transduction 被引量:1
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作者 LI Qing-hua FAN Tian-xue +2 位作者 PANG Tian-xiang YUAN Wen-su HAN Zhong-chao 《Chinese Medical Journal》 SCIE CAS CSCD 2006年第18期1536-1542,共7页
Background Sam68 plays an important role as a multiple functional RNA binding nuclear protein in cell cycle progress, RNA usage, signal transduction, and tyrosine phosphorylation by Src during mitosis. However, its pr... Background Sam68 plays an important role as a multiple functional RNA binding nuclear protein in cell cycle progress, RNA usage, signal transduction, and tyrosine phosphorylation by Src during mitosis. However, its precise impact on these essential cellular functions remains unclear. The purpose of this study is to further elucidate Sam68 functions in RNA metabolism, signal transduction regulation of cell growth and cell proliferation in DT40 cell line. Methods By using gene targeting method, we isolated a mutation form of Sam68 in DT40 cells and described its effect on cell growth process and signal transduction. Southern, Northern, and Western blot, phosphorylation and flow-cytometric analyses were performed to investigate the Sam68 functions. Results A slower growth rate (2.1 hours growth elongation) and longer S phase (1.7 hours elongation) was observed in the Sam68 mutant cells. Serum depletion resulted in increased amounts of dead cells, and expansion of S phase in mutant cells. Upon B cell cross-linking, the maximal level of tyrosine phosphorylation on BLNK was observed to be significantly lower in mutant cells.Conclusions The proline rich domain of Sam68 is involved in cell growth control by modulating the function of mRNAs in S phase or earlier and the functions as an adaptor molecule in B cell signal transduction pathways. 展开更多
关键词 Sam68 RNA binding protein signal transduction cell death tyrosine phosphorylation
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The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases 被引量:2
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作者 Yuan CHEN Qi TIAN 《Frontiers of Medicine》 SCIE CSCD 2011年第1期70-76,共7页
Protein kinase C epsilon(PKCε)is one of major isoforms in novel PKC family.Although it has been extensively characterized in the past decade,the role of PKCεin neuron is still not well understood.Advances in molecul... Protein kinase C epsilon(PKCε)is one of major isoforms in novel PKC family.Although it has been extensively characterized in the past decade,the role of PKCεin neuron is still not well understood.Advances in molecular biology have now removed significant barriers to the direct investigation of PKCεfunctions in vivo,and PKCεhas been increasingly implicated in the neural biological functions and associated neurogenic diseases.Recent studies have provided important insights into the influence of PKCεon cortical processing at both the single cell level and network level.These studies provide compelling evidence that PKCεcould regulate distinct aspects of neural signal transduction and suggest that the coordinated actions of a number of molecular signals contribute to the specification and differentiation of PKCεsignal pathway in the developing brain. 展开更多
关键词 protein kinase signal transduction neurogenic disease
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Modulating protein kinase D1 signal transduction
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作者 ZHANG Wei XU Jian JIA Chang-ku ZHENG Shu-sen 《Chinese Medical Journal》 SCIE CAS CSCD 2009年第15期1816-1820,共5页
Protein kinase C (PKC) consists of a family of serine/threonine kinases that are identified by the presence of two copies of the C1 domain, which form the diacylglycerol (DAG)-binding module. According to their en... Protein kinase C (PKC) consists of a family of serine/threonine kinases that are identified by the presence of two copies of the C1 domain, which form the diacylglycerol (DAG)-binding module. According to their enzymatic activities PKCs are sub-divided into conventional isozymes (PKCα, β and γ; calcium, phospholipid and DAG-activated kinases), novel isozymes (PKCδ, ε, η, μ and θ; calcium-insensitive, phospholipid-dependent and DAG-dependent), and atypical isozymes (PKCζ and λ; calcium-insensitive and DAG-insensitive enzymes). Human protein kinase Cμ and its mouse homolog, protein kinase D1 (PKD1), which has been under intense investigation in recent years, is a DAG-dependent, Ca^2+-independent serine/threonine protein kinase as a novel PKC isoform. Recently PKDs were classified as a novel subgroup of the calcium/calmodulin-dependent protein kinase (CAMK) family, based on sequence similarities of the kinase domain; the catal^ctic domain of PKD1 has the highest homology to CAMK. PKD1 has three main pathways for activation. One is DAG-phospholipase C (PLC)-PKC-dependent activation of PKD1. In this model, PKD 1 not only acts as a direct DAG target but also lies downstream of PKCs to regulate biological processes in cells. 展开更多
关键词 protein kinase D signal transduction APOPTOSIS SURVIVAL
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膀胱癌100例血清Zeste基因增强子同源物2和信号传导蛋白3表达水平及诊断价值分析
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作者 吴娟 王丹 +1 位作者 张前进 裴兵 《安徽医药》 CAS 2024年第10期2035-2038,共4页
目的探讨膀胱癌病人血清Zeste基因增强子同源物2(EZH2)和信号传导蛋白3(SMAD3)表达水平及临床意义。方法纳入江苏省人民医院宿迁医院于2021年1月至2022年12月收治的膀胱癌病人进行研究(100例),另选取同期于该院就诊的泌尿系统良性疾病... 目的探讨膀胱癌病人血清Zeste基因增强子同源物2(EZH2)和信号传导蛋白3(SMAD3)表达水平及临床意义。方法纳入江苏省人民医院宿迁医院于2021年1月至2022年12月收治的膀胱癌病人进行研究(100例),另选取同期于该院就诊的泌尿系统良性疾病病人作为良性疾病组(93例)以及健康体检者作为对照(100例)。采用Pearson相关性分析法分析膀胱癌病人血清中EZH2和SMAD3表达水平的相关性;采用logistic多因素回归分析法分析膀胱癌发生的影响因素;采用ROC曲线分析EZH2和SMAD3对膀胱癌的诊断效能。结果膀胱癌病人血清中EZH2(101.34±15.09)ng/L和SMAD3(226.53±25.94)ng/L表达水平均高于良性疾病组(85.96±11.23)ng/L、(203.11±22.18)ng/L和对照组(83.91±9.14)ng/L、(198.03±20.30)ng/L(均P<0.001);膀胱癌病人血清EZH2和SMAD3表达水平呈正相关(r=0.72,P<0.001);膀胱癌组年龄≥60岁(74/187)、有吸烟史的病人(76/166)所占比例均高于良性疾病组(65/187、55/166)及对照组(48/187、35/166)(均P<0.05);年龄、吸烟史、EZH2、SMAD3为发生膀胱癌的危险因素(P<0.05);以良性疾病组为对照,血清EZH2和SMAD3单独检测诊断膀胱癌的曲线下面积(AUC)分别为0.78、0.78,二者联合检测的AUC为0.85,优于各自单独检测(Z_(二者联合-EZH2)=2.81、Z_(二者联合-SMAD3)=2.68,P=0.009、0.007)。结论血清EZH2和SMAD3与膀胱癌的发生有关,二者联合对膀胱癌具有一定的诊断价值。 展开更多
关键词 膀胱肿瘤 Zeste基因增强子同源物2 信号传导蛋白3 诊断价值 表达水平
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植物异三聚体G蛋白研究进展
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作者 尚忠林 康二芳 +1 位作者 李雨珂 付玉 《河北师范大学学报(自然科学版)》 CAS 2024年第1期9-18,共10页
植物细胞中的异三聚体G蛋白信号转导系统包括异三聚体G蛋白、G蛋白偶联受体、类受体激酶、G蛋白信号调节因子等,这些信号转导组分在感受物理及化学刺激、启动细胞内信号级联反应、调控细胞内代谢和基因表达过程中发挥重要作用.异三聚体... 植物细胞中的异三聚体G蛋白信号转导系统包括异三聚体G蛋白、G蛋白偶联受体、类受体激酶、G蛋白信号调节因子等,这些信号转导组分在感受物理及化学刺激、启动细胞内信号级联反应、调控细胞内代谢和基因表达过程中发挥重要作用.异三聚体G蛋白参与调控植物生长发育(如胚胎形成、营养器官生长、有性生殖等)、植物对生物及非生物胁迫的响应、根瘤形成等过程.因此,异三聚体G蛋白信号系统组分参与调控多种农作物的农艺性状,并最终影响农产品的产量和品质.对植物异三聚体G蛋白的结构、活化机制和生理功能等方面近年来取得的研究进展进行了回顾和总结. 展开更多
关键词 异三聚体G蛋白 生长发育 胁迫耐受 信号转导
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多囊卵巢综合征患者卵巢颗粒细胞胰岛素抵抗的相关信号通路 被引量:1
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作者 任露露 任文超 +1 位作者 张晓轩 任春娥(审校) 《国际生殖健康/计划生育杂志》 CAS 2024年第1期32-37,共6页
胰岛素抵抗(insulin resistance,IR)与多囊卵巢综合征(polycystic ovary syndrome,PCOS)的发生发展有关,而与IR相关的胰岛素信号通路异常会引起卵巢局部代谢紊乱,进而影响卵泡发育及卵子质量。PCOS卵巢颗粒细胞中胰岛素作用的经典通路,... 胰岛素抵抗(insulin resistance,IR)与多囊卵巢综合征(polycystic ovary syndrome,PCOS)的发生发展有关,而与IR相关的胰岛素信号通路异常会引起卵巢局部代谢紊乱,进而影响卵泡发育及卵子质量。PCOS卵巢颗粒细胞中胰岛素作用的经典通路,包括磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)通路和丝裂原激活的蛋白激酶(mitogen-activated protein kinase,MAPK)/细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)通路;与炎症相关的通路包括Toll样受体(Toll-like receptor,TLR)/核因子κB(nuclear factor-κB,NF-κB)通路等;氧化应激相关通路包括核转录因子红系2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)/血红素加氧酶-1(heme oxygenase-1,HO-1)途径和GTP酶免疫相关蛋白7(GTPase of immunity-associated protein 7,GIMAP7)/音猬因子(sonic hedgehog,SHH)途径;与脂质代谢相关的通路如激活转录因子4(activating transcription factor 4,ATF4)通路等。明确PCOS患者卵巢颗粒细胞中IR相关信号转导通路,增进PCOS病理生理机制的认识,进一步为PCOS的治疗提供新思路。 展开更多
关键词 多囊卵巢综合征 胰岛素抵抗 细胞内信号肽和蛋白质类 信号传导 颗粒细胞
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淋巴细胞胞质蛋白2在恶性肿瘤发生与发展过程中的免疫调节机制
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作者 魏琳 韩英伦 刘欣 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2024年第1期10-17,共8页
淋巴细胞胞质蛋白2(lymphocyte cytosolic protein 2,LCP2)是一种衔接蛋白质,在T细胞受体信号通路中扮演重要角色,激活下游信号因子以完成机体的免疫应答过程。LCP2也在恶性肿瘤的发生发展与转移中发挥重要作用,其高表达会导致不良的预... 淋巴细胞胞质蛋白2(lymphocyte cytosolic protein 2,LCP2)是一种衔接蛋白质,在T细胞受体信号通路中扮演重要角色,激活下游信号因子以完成机体的免疫应答过程。LCP2也在恶性肿瘤的发生发展与转移中发挥重要作用,其高表达会导致不良的预后效果,降低患者生存率,其具体作用机制涉及多条信号通路。本文不仅对LCP2的分子结构以及基本功能进行了介绍,而且重点综合评述了LCP2通过参与NF-κB、MAPK、JAK/STAT以及PD-1/PD-L1信号通路调控恶性肿瘤发生与发展的分子机制。总结了LCP2作为肿瘤治疗靶点的潜在作用,为将来用于相关疾病的诊断、治疗和标志物筛选等提供理论基础和参考依据。 展开更多
关键词 淋巴细胞胞质蛋白2 衔接蛋白质 信号通路 恶性肿瘤
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蛋白质翻译后修饰对环磷酸鸟苷-腺苷酸合成酶功能的调控
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作者 申梦阳 路晨 +3 位作者 王怡 裴金勇 王洁 杨波 《新乡医学院学报》 CAS 2024年第8期701-705,共5页
环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子信号通路是细胞感知细胞质中异常存在的双链DNA的主要效应器,对于该信号通路的调节,可以通过调控细胞质内DNA识别受体环磷酸鸟苷-腺苷酸合成酶的功能来完成。近年来研究发现,蛋白质翻译后修... 环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子信号通路是细胞感知细胞质中异常存在的双链DNA的主要效应器,对于该信号通路的调节,可以通过调控细胞质内DNA识别受体环磷酸鸟苷-腺苷酸合成酶的功能来完成。近年来研究发现,蛋白质翻译后修饰,包括磷酸化、乙酰化、泛素化、甲基化、类泛素修饰等在固有免疫信号通路的调节中具有重要功能。本文就蛋白质翻译后修饰如何通过不同的机制对环磷酸鸟苷-腺苷酸合成酶的功能及其下游的信号通路产生多种多样的影响进行阐述。 展开更多
关键词 蛋白质翻译后修饰 环磷酸鸟苷-腺苷合成酶 信号转导 固有免疫
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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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AMPK:多样性调控机制与疾病治疗新视角 被引量:1
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作者 宁静华 张鑫 张钰哲 《中国比较医学杂志》 CAS 北大核心 2024年第2期167-178,共12页
单磷酸腺苷激活的蛋白激酶(AMP-activated protein kinase,AMPK)是一种保守的细胞能量感受器,在调控细胞生长、增殖、分化、自噬、磷酸化、串扰以及葡萄糖和脂质代谢等方面起着重要作用,当机体能量匮乏或某些极端情况时AMPK被激活,而在... 单磷酸腺苷激活的蛋白激酶(AMP-activated protein kinase,AMPK)是一种保守的细胞能量感受器,在调控细胞生长、增殖、分化、自噬、磷酸化、串扰以及葡萄糖和脂质代谢等方面起着重要作用,当机体能量匮乏或某些极端情况时AMPK被激活,而在营养过剩时被抑制,以维持能量平衡。此外,AMPK信号通路介导铁死亡发生的调控机制也体现了其独特作用,AMPK在不同细胞器里发挥特殊调控功能为疾病治疗提供了新的方向。这也是预防疾病的治疗靶标,如生殖系统疾病、衰老、癌症、炎症和心脏功能障碍等。该文综述了细胞能量不平衡对机体微环境造成的损害,AMPK通过多样性信号调控机制激发了其在疾病和药物中的潜在治疗潜力,为不同系统疾病提供了治疗新思路。通过综述AMPK信号通路的多样性调节机制,为靶向AMPK的癌症治疗和其他疾病的治疗提供理论参考。 展开更多
关键词 单磷酸腺苷激活的蛋白激酶 能量代谢 铁死亡 信号传导 治疗靶标
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小分子药物治疗骨关节炎的热点问题及应用前景
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作者 余帅 刘家伟 +6 位作者 朱彬 潘檀 李兴龙 孙广峰 于海洋 丁亚 王宏亮 《中国组织工程研究》 CAS 北大核心 2025年第9期1913-1922,共10页
背景:骨关节炎的病理生理过程中存在多种蛋白、信号通路及炎症递质等的参与,开发针对这些蛋白、信号通路及炎症递质等的小分子药物,可有效延缓骨关节炎的进展并改善其临床表现。目的:基于骨关节炎的发病机制,对小分子药物治疗骨关节炎... 背景:骨关节炎的病理生理过程中存在多种蛋白、信号通路及炎症递质等的参与,开发针对这些蛋白、信号通路及炎症递质等的小分子药物,可有效延缓骨关节炎的进展并改善其临床表现。目的:基于骨关节炎的发病机制,对小分子药物治疗骨关节炎的研究进展作一综述。方法:检索PubMed、中国知网和万方数据库,英文检索词为“osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents”,中文检索词为“骨关节炎,小分子药物,小分子抑制剂”,按纳入和排除标准共纳入68篇文献进行总结。结果与结论:①目前对于骨关节炎发病机制的研究尚不明确,骨关节炎的发生发展与蛋白质、细胞因子及信号转导通路的关系较为密切,因此其治疗机制较为复杂,当前通过小分子药物靶向骨关节炎相关的蛋白质、细胞因子及信号转导通路成为一大研究热点。②小分子药物通常具有明确的细胞内或细胞外靶点和疗效,包括增强软骨修复、抑制关节退化、减轻炎症和缓解疼痛,另外一些抗骨关节炎的小分子药物在促进干细胞软骨分化和软骨基质重建方面显示出前景。③目前对于小分子药物靶向骨关节炎的病理生理过程从而延缓骨关节炎的进展,还处于实验性阶段,但这些小分子药物在实验过程中大部分都表现出预期的结果,目前并无相关研究说明小分子药物治疗骨关节炎的疗效。④小分子药物治疗骨关节炎在基础实验阶段已经达到了预期的实验结果,大量研究表明,小分子药物可以靶向抑制引起骨关节炎的特定蛋白质、细胞因子及信号转导通路,从而治疗骨关节炎,但其安全性和有效性等问题还需要进一步的基础和临床研究进行验证,这一过程需要更多的学者进行探索和研究。⑤目前国内外有许多学者针对骨关节炎的治疗做出了贡献,比起传统治疗方式而言,小分子药物在基础实验阶段表现出更好的疗效和安全性,有望成为未来骨关节炎治疗的新兴方法,为骨关节炎患者摆脱痛苦。 展开更多
关键词 骨关节炎 退行性骨关节病 蛋白质 细胞因子 信号转导通路 靶向治疗 炎症 软骨修复 小分子药物 综述
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