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红景天甙对肝纤维化大鼠肝组织ROCK表达的影响 被引量:16
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作者 吴晓玲 曾维政 +3 位作者 蒋明德 秦建平 徐辉 王钊 《世界华人消化杂志》 CAS 北大核心 2009年第8期765-769,共5页
目的:研究红景天甙对肝纤维化大鼠肝组织ROCK基因表达的影响,了解其干预肝纤维化的机制.方法:健康雄性SD大鼠,随机分为3组:对照组(n=10),红景天甙干预组(n=40)和肝纤维化模型组(n=40).大鼠肝纤维化采用CCl4皮下注射法(300mL/L,3mL/kg,每... 目的:研究红景天甙对肝纤维化大鼠肝组织ROCK基因表达的影响,了解其干预肝纤维化的机制.方法:健康雄性SD大鼠,随机分为3组:对照组(n=10),红景天甙干预组(n=40)和肝纤维化模型组(n=40).大鼠肝纤维化采用CCl4皮下注射法(300mL/L,3mL/kg,每周2次,共8wk)诱导.红景天甙干预采用腹腔注射法,剂量5mg/kg,每周2次.肝脏胶原沉积状况采用Masson胶原染色以及HE染色观察,ROCKⅠ、ROCKⅡ表达水平分别采用原位杂交(in situ hybridization,ISH)和免疫组化(im munohistochemistry,IH)方法检测.实验图像经电子计算机扫描,数据采用专业图像分析软件统计分析.结果:肝纤维化大鼠肝脏肝细胞坏死、再生明显,假小叶形成,胶原纤维沉积明显增加,肝实质结构紊乱.红景天甙干预组大鼠肝组织胶原沉积明显减少,组织学积分平均胶原面积降低(2.1±0.3vs3.6±0.8,74.82±21.51μm2vs290.86±89.37μm2,均P<0.05).与模型组比较,红景天甙干预性治疗组ROCKⅠ,Ⅱ蛋白表达水平均明显下降(0.203±0.068vs0.357±0.182,0.237±0.056vs0.394±0.238,均P<0.05),ROCKⅠ,ⅡmRNA表达水平明显下降(0.197±0.019vs0.394±0.238,0.185±0.031vs0.279±0.112,均P<0.01).结论:红景天甙可能通过调节Rho-ROCK信号传导通路,减少肝脏胶原纤维的合成与沉积,有效干预CCl4诱导的大鼠肝纤维化. 展开更多
关键词 红景天甙 肝纤维化 Rho相关卷曲螺旋形 成蛋白激酶 肝脏 大鼠 原位杂交法
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Involvement of MAPK/ERK kinase-ERK pathway in exogenous bFGF-induced Egr-1 binding activity enhancement in anoxia-reoxygenation injured astrocytes
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作者 刘颖 陆锦标 +1 位作者 陈琦 叶诸榕 《Neuroscience Bulletin》 SCIE CAS CSCD 2007年第4期221-228,共8页
Objective Intravenous administration of basic fibroblast growth factor (bFGF) is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, es... Objective Intravenous administration of basic fibroblast growth factor (bFGF) is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, especially the signal transduction pathways, involved in this protective role of bFGF. Methods Anoxia-reoxygenation treated atrocytes were used to study the role of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MAPK/ERK kinase, MEK)-ERK signaling pathway after exogenous bFGF administration by Western blot. Electrophoretic mobile shift assay was used to detect the binding activity of early growth response factor-1 (Egr-1), an important transcription factor for endogenous bFGF. Results bFGF could protect some signal transduction proteins from the oxygen-derived free radicals induced degradation. ERK1/2 was activated and involved in Egr-1 binding activity enhancement induced by exogenous bFGF. Conclusion MEK-ERK MAPK cascade may be an important signal transduction pathway contributed to bFGF induced enhancement of Egr-1 binding activity in anoxia-reoxygenation injured astrocytes. 展开更多
关键词 extracellular signal-regulated kinase mitogen-activated protein kinase free radicals fibroblast growth factor 2 early growth response protein 1 ASTROCYTE
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INHIBITION OF MELATONIN BIOSYNTHESIS ACTIVATES PROTEIN KINASE A AND INDUCES ALZHEIMER-LIKE TAU HYPERPHOSPHORYLATION IN RATS 被引量:3
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作者 Ling-qiangZhu Shao-huiWang Zhi-qunLing QunWang Mao-qiongHu Jian-zhiWang 《Chinese Medical Sciences Journal》 CAS CSCD 2005年第2期83-87,共5页
Objective To investigate effect of inhibiting melatonin biosynthesis on activities of protein kinase A (PKA), glycogen synthase kinase-3 (GSK-3) and tau phosphorylation at PS214 and M4 epitopes using haloperidol, a sp... Objective To investigate effect of inhibiting melatonin biosynthesis on activities of protein kinase A (PKA), glycogen synthase kinase-3 (GSK-3) and tau phosphorylation at PS214 and M4 epitopes using haloperidol, a specific inhibitor of 5-hydroxyindole-O-methyltransferase. Methods Brain ventricular and intraperitoneal injections were used for haloperidol administration, Western blots for tau phosphorylation, 32P-labeling for PKA and GSK-3 activity, and high performance liquid chromatograph for detection of serum melatonin levels. Results Haloperidol injection through the lateral ventricle and intraperitoneal reinforcement significantly stimulated PKA activity with a concurrent hyperphosphorylation of tau at M4 (Thr231/Ser235) and PS214 (Ser214) sites. Prior treatment of the rats using melatonin supplement for one week and reinforcement during the haloperidol administration arrested PKA activity and attenuated tau hyperphosphorylation. GSK-3 activity showed no obvious change after haloperidol injection, however, melatonin supplements and reinforcements during haloperidol infusion inactivated basal activity of GSK-3. Conclusion Decreased melatonin may be involved in Alzheimer-like tau hyperphosphorylation, and overactivation of PKA may play a crucial role in this process. 展开更多
关键词 Alzheimer's disease HALOPERIDOL MELATONIN TAU protein kinase A
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Protein kinase A suppresses the differentiation of 3T3-L1 preadipocytes 被引量:1
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作者 Li,F Wang,D +4 位作者 Zhou,Y Zhou,B Yang,Y Chen,H Song,J 《Cell Research》 SCIE CAS CSCD 2008年第2期311-323,共13页
cAMP and protein kinase A (PKA) are widely known as signaling molecules that are important for the induction of adipogenesis. Here we show that a strong increase in the amount of cAMP inhibits the adipogenesis of 3T... cAMP and protein kinase A (PKA) are widely known as signaling molecules that are important for the induction of adipogenesis. Here we show that a strong increase in the amount of cAMP inhibits the adipogenesis of 3T3-L1 fibroblast cells. Stimulation of PKA activity suppresses adipogenesis and, in contrast, inhibition of PKA activity markedly accelerates the adipogenic process. As adipogenesis progresses, there is a significant increase in the expression level of PKA regulatory and a corresponding decrease in PKA activity. Moreover, treatment of 3T3-L1 cells with epidermal growth factor (EGF) stimulates PKA activity and blocks adipogenesis. Inhibition of PKA activity abolishes this suppressive effect of EGF on adipogenesis. Moreover, asubunits ctivation of PKA induces serine/threonine phosphorylation, reduces tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and the association between PKA and IRS-1. Taken together, our study demonstrates that PKA has a pivotal role in the suppression of adipogenesis, cAMP at high concentrations can suppress adipogenesis through PKA activation. These findings could be important and useful for understanding the mechanisms of adipogenesis and the relevant physiological events. 展开更多
关键词 cAMP PKA ADIPOCYTE ADIPOGENESIS C/EBP PPAR
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Occurrence of cGMP/nitric oxide-sensitive store-operated calcium entry in fibroblasts and its effect on matrix metalloproteinase secretion 被引量:1
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作者 Yong Huang Min-Qiang Lu Hua Li Chi Xu Shu-Hong Yi Gui-Hua Chen 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第34期5483-5489,共7页
AIM: To examine the existence of Nitric oxide/ cGMP sensitive store-operated Ca^2+ entry in mouse fibroblast NIH/3T3 cells and its influence on matrix metalloproteinase (MMP) production and adhesion ability of fib... AIM: To examine the existence of Nitric oxide/ cGMP sensitive store-operated Ca^2+ entry in mouse fibroblast NIH/3T3 cells and its influence on matrix metalloproteinase (MMP) production and adhesion ability of fibroblasts. METHODS: NIH/3T3 cells were cultured. Confocal laser scanning microscopy was used to examine the existence of thapsigargin-induced store-operated Ca^2+ entry in fibroblasts. Gelatin zymography and semiquantitative reverse transcriptase-polymerase chain reaction (RTPCR) were employed to detect the involvement of [Ca^2+]i and NO/cGMP in MMP secretion. The involvement of NO/ cGMP-sensitive Ca^2+ entry in adhesion was determined using matrigel-coated culture plates. RESULTS: 8-bromo-cGMP inhibited the thapsigargin-induced Ca^2+ entry in 3T3 cells. The cGMP-induced inhibition was abolished by an inhibitor of protein kinase G, KT5823 (1μmol/L). A similar effect on the Ca^2+ entry was observed in 3T3 cells in response to a NO donor, (±)-S-nitroso-N-acetylpenicillamine (SNAP). The inhibitory effect of SNAP on the thapsigargin-induced Ca^2+ entry was also observed, indicating NO/cGMP-regulated Ca^2+ entry in 3T3 cells. Results of gelatin zymography assay showed that addition of extracellular Ca^2+ concentration induced MMP release and activation in a dose-dependent manner. RT-PCR also showed that cGMP and SNAP reduced the production of MMP mRNA in 3T3 cells. Experiments investigating adhesion potentials demonstrated that cGMP and SNAP could upgrade 3T3 cell attachment rate to the matrigel-coated culture plates.CONCLUSION: NO/cGMP sensitive store-operated Ca^2+ entry occurs in fibroblasts, and attenuates their adhesion potentials through its influence on MMP secretion. 展开更多
关键词 CGMP Nitric oxide Protein kinase G Storeoperated Ca^2+ entry Matrix metalloproteinase FIBROBLAST
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FGF-receptor substrate 2 functions as a molecular sensor ntegrating external regulatory signals into the FGF pathway 被引量:2
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作者 Wenchao Zhou Xiujing Feng +3 位作者 Yingjie Wu Johannes Benge Zhe Zhang Zhengjun Chen 《Cell Research》 SCIE CAS CSCD 2009年第10期1165-1177,共13页
Fibroblast growth factor (FGF) receptor substrate 2a (FRS2α) is the main mediator of signaling in the FGF pathway. Recent studies have shown that mitogen-activated protein kinase (MAPK) phosphorylates serine an... Fibroblast growth factor (FGF) receptor substrate 2a (FRS2α) is the main mediator of signaling in the FGF pathway. Recent studies have shown that mitogen-activated protein kinase (MAPK) phosphorylates serine and threonine residues in FRS2, negatively affecting FGF-induced tyrosine phosphorylation (PY) of FRS2. Several kinds of stimuli can induce serine/threonine phosphorylation (PS/T) of FRS2, indicating that FRS2 may be useful for studying crosstalk between growth factor signaling pathways. Here, we report that FGF-induced PY of FRS2 can be attenuated by EGF co-stimulation in PC12cells; this inhibitory effect could be completely reversed by U0126, an inhibitor of MEK. We further identified the ERK1/2-binding motif in FRS2 and generated FRS2-3KL, a mutant lacking MAPK binding and PT upon FGF and/or EGF stimulation. Unlike wild-type (WT) FRS2, FGF-induced PY of FRS2-3KL could not be inhibited by EGF co-stimulation, and FRS2-3KL-expressing PC12 cells exhibited more differentiating potential than FRS2-WT-expressing cells in response to FGF treatment. These results suggest that PS/T of FRS2 mediated by the FRS2-MAPK negative regulatory loop may function as a molecular switch integrating negative regulatory signals from other pathways into FGFR-generated signal transduction. 展开更多
关键词 fibroblast growth factor (FGF) epithelial growth factor (EGF) crosstalk threonine phosphorylation CO-STIMULATION
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Specific activation of 2'-5'oligoadenylate synthetase gene promoter by hepatitis C virus-core protein:A potential for developing hepatitis C virus targeting gene therapy
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作者 Ying Wang Shan-Shan Mao +3 位作者 Qiong-Qiong He Yuan Zi Ji-Fang Wen De-Yun Feng 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第25期3178-3182,共5页
AIM: TO examine whether 2'-5'oligoadenylate synthetase (OAS) gene promoter can be specifically activated by hepatitis C virus (HCV)-core protein. METHODS: Human embryo hepatic cell line L02 was transfected wit... AIM: TO examine whether 2'-5'oligoadenylate synthetase (OAS) gene promoter can be specifically activated by hepatitis C virus (HCV)-core protein. METHODS: Human embryo hepatic cell line L02 was transfected with pcDNA3.1-core plasmid and selected by G418. Expression of HCV-core was detected by reverse transcription polymerase chain reaction and Western blotting. The OAS promoter sequence was amplified from the genomic DNA and inserted into pGL3-basic vector. The resultant pGL3-OAS-Luci plasmid was transiently transfected into L02/core cells and luciferase activity was assayed. I^ESULTS: L02/core cell line stably expressing HCV- core protein was established. The pGL3-OAS-Luci construct exhibited significant transcriptional activity in the L02/core cells but not in the L02 cells. CONCLUSION: HCV-core protein activates the OAS gene promoter specifically and effectively. Utilization of OAS gene promoter would be an ideal strategy for developing HCV-specific gene therapy. 展开更多
关键词 Hepatitis C virus Gene promoter Gene therapy CORE 2'-5'oligoadenylate synthetase
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