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排序方式: 共有1436条查询结果,搜索用时 31 毫秒
1.
Alessia Pascale Marialaura Amadio Stefano Govoni Fiorenzo Battaini 《Pharmacological research》2007,55(6):560-569
The brain represents the primary centre for the regulation and control of all our body activities, receiving and interpreting sensory impulses and transmitting information to the periphery. Most importantly, it is also the seat of consciousness, thought, emotion and especially memory, being in fact able to encode, store and recall any information. Memory is really what makes possible so many of our complex cognitive functions, including communication and learning, and surely without memory, life would lose all of its glamour and purpose. Age-associated mental impairment can range in severity from forgetfulness at the border with pathology to dementia, such as in Alzheimer's disease. In recent years, one of the most relevant observations of research on brain aging relates to data indicating that age-related cognitive decline is not only due to neuronal loss, as previously thought; instead, scientists now believe that age-associated functional changes have more to do with the dysfunctions occurring over time. Within this context a prominent role is certainly played by signal transduction cascades which guarantee neuronal cell to elaborate coordinated responses to the multiple signals coming from the outside and to adapt itself to the environmental changes and requests. This review will focus the attention on protein kinase C pathway, with a particular interest on its activation process, and on the role of protein-lipid and protein-protein interactions to selectively localize the cellular responses. Furthermore, information is emerging and will be discussed on the possibility of mRNA stabilization through PKC activation. This review will also approach the issue on how alterations of these molecular cascades may have implications in physiological and pathological brain aging, such as Alzheimer's disease. 相似文献
2.
目的研究柴胡疏肝散、四君子汤对肝郁、脾虚大鼠Th细胞蛋白激酶C(PKC)表达的影响及其意义。方法应用RT—PCR法研究柴胡疏肝散、四君子汤对Th细胞PKCmRNA表达的影响。结果脾虚时PKCmRNA表达水平明显低于正常对照组 (P <0 .0 5 ) ,四君子汤治疗后恢复正常 (P <0 .0 5 ) ,柴胡疏肝散治疗后仍明显低于正常对照组 ;肝郁时PKCmRNA表达水平明显高于正常对照组 (P <0 .0 5 ) ,柴胡疏肝散治疗后恢复正常 (P <0 .0 5 ) ,但四君子汤治疗效应不明显。结论肝脾两脏在T细胞尤其是Th0的活化中具有相关性 ;PKC参与了肝脾这种相关的发生。 相似文献
3.
4.
卵巢癌中蛋白激酶C的表达及其临床意义 总被引:2,自引:0,他引:2
目的 探讨上皮性卵巢癌组织蛋白激酶C (proteinkinaseC ,PKC)的表达和化疗耐药的关系 ,以及与P -糖蛋白 (P -gp)的相关性。方法 用免疫组化S -P法检测 35例卵巢上皮性肿瘤组织、 2 0例卵巢良性肿瘤组织和 2 0例正常卵巢组织中PKC和P -gp的表达 ,并进行相关临床因素分析。结果 ①PKC、P -gp在卵巢恶性肿瘤中的表达明显高于在良性及正常组织中的表达 ;并且PKC和P -gp的表达有相关性 (P <0 0 5 ) ;②卵巢癌PKC的表达与临床病理因素无直接关系 ;③恶性肿瘤中 ,初治和复发的PKC表达阳性率分别为 34 8%和 75 % ;④化疗对PKC表达阳性和阴性卵巢癌患者的有效率分别为 2 3 5 %、 6 6 7% (P <0 0 5 ) ;⑤PKC表达阴性患者的预后优于阳性者 (P =0 0 39)。结论 PKC表达与卵巢癌组织化疗耐药明显相关 ,可能在P -gp介导的卵巢癌多药耐药中起重要作用。 相似文献
5.
6.
目的 :观察雌性大鼠行去势后以及雌激素替代治疗海马结构蛋白激酶C ( proteinkinaseC ,PKC)阳性细胞的变化 ,通过该模型研究绝经期后女性情绪烦躁、记忆下降等神经精神症状的分子机制。方法 :将大鼠分为对照组、去势 3个月组和去势后雌激素替代治疗 3个月组 ,用免疫组织化学方法检测海马结构PKC阳性细胞的变化。结果 :PKC阳性细胞主要分布于下托和齿状回的颗粒层 ,其中齿状回内的阳性细胞较下托的多。去势 3个月组与对照组相比 ,齿状回内的PKC阳性细胞没有显著性减少 (P >0 .0 5 ) ,下托PKC阳性细胞显著减少 (P <0 .0 5 ) ;雌激素治疗组与对照组相比 ,下托细胞数量有所减少 ,但无显著性差异 (P >0 .0 5 )。结论 :海马结构下托PKC阳性细胞的减少可能在绝经后女性情绪烦躁、记忆下降等症状中起重要的作用。 相似文献
7.
Objective: This study investigated the effects of insulin on the phagocytosis of C3bi – and IgG-opsonized yeast particles in normal
human neutrophils.
Methods: Neutrophils were incubated in different insulin concentrations for 30 minutes and stimulated by C3bi – or IgG-opsonized yeast
particles. Phagocytosis was quantified by both light microscopy and FACscan flow cytometry. Laser confocal microscopy was
used for quantification of F-actin levels.
Results: Elevated insulin concentrations decreased neutrophil phagocytosis of both types of targets. This defect was shown to be in
part due to a delayed phagocytosis in the presence of insulin. Following a 30 minute incubation, insulin was found to increase
the accumulation of cortical F-actin, without affecting the total cellular F-actin content. The specific PKCα/β inhibitor,
Go6976, abolished the insulin-mediated increase in cortical F-actin content and both Go6976 and the PKCα/β/δ/ε-specific inhibitor
GF109203X reversed the inhibitory effects of insulin on phagocytosis.
Conclusion: Hyperinsulinemia in vitro can inhibit phagocytosis of opsonized targets in normal human neutrophils. This effect of insulin is dependent on activation
of PKCα and/or PKCβ, and these insulin signals may interfere with the dynamic assembly/disassembly and/or distribution of
F-actin, which is required for the phagocytosis process.
Received 8 July 2005; accepted 13 October 2005 without revision I. Ahnfelt-R?nne 相似文献
8.
Autocrine motility factor (AMF) is one of the motility cytokines regulating tumor cell migration, therefore identification
of the signaling pathway coupled with it has critical importance. Previous studies revealed several elements of this pathway
predominated by lipoxygenase-PKC activations but the role for tyrosine kinases remained questionable. Motility cytokines frequently
have mitogenic effect as well, producing activation of overlapping signaling pathways therefore we have used B16a melanoma
cells as models where AMF has exclusive motility effect. Our studies revealed that in B16a cells AMF initiated rapid (1–5
min) activation of the protein tyrosine kinase (PTK) cascade inducing phosphorylation of 179, 125, 95 and 40/37 kD proteins
which was mediated by upstream cyclo- and lipoxygenases. The phosphorylated proteins were localized to the cortical actin-stress
fiber attachment zones in situ by confocal microscopy. On the other hand, AMF receptor activation induced significant decrease
in overall serine-phosphorylation level of cellular proteins accompanied by serine phosphorylation of 200, 90, 78 and 65 kd
proteins. The decrease in serine phosphorylation was independent of PTKs, PKC as well as cyclo- and lipoxygenases. However,
AMF induced robust translocation of PKCα to the stress fibers and cortical actin suggesting a critical role for this kinase
in the generation of the motility signal. Based on the significant decrease in serine phosphorylation after AMF stimulus in
B16a cells we postulated the involvement of putative serine/threonine phosphatase(s) upstream lipoxygenase and activation
of the protein tyrosine kinase cascade downstream cyclo- and lipoxygenase(s) in the previously identified autocrine motility
signal.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
9.
Philip J. Bergman Karen R. Gravitt Nancy E. Ward Pedro Beltran Krishna P. Gupta Catherine A. O'Brian 《Investigational new drugs》1997,15(4):311-318
Phorbol ester protein kinase C (PKC) activators and PKC isozyme over-expression have been shown to significantly reduce intracellular accumulation of chemotherapeutic drugs, in association with the induction of multidrug resistance (MDR) in drug-sensitive cancer cells and enhancement of drug resistance in MDR cancer cells. These observations constitute solid evidence that PKC plays a significant role in the MDR phenotype of cancer cells. PKC-catalyzed phosphorylation of the drug-efflux pump P-glycoprotein was recently ruled out as a contributing factor in MDR. At present, the sole drug transport-related event that has been identified as a component of the role of PKC in MDR is PKC-induced expression of the P-glycoprotein-encoding gene mdr1. The objective of this study was to test the hypothesis that PKC can modulate the uptake of chemotherapeutic drugs in cancer cells independently of P-glycoprotein. We analyzed the effects of selective PKC activators/inhibitors on the uptake of radiolabelled cytotoxic drugs by cultured human colon cancer cells that lacked P-glycoprotein activity and did not express the drug efflux pump at the level of message (mdr1) or protein. We found that the selective PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) significantly reduced uptake of [14C] Adriamycin and [3H] vincristine in human colon cancer cells devoid of P-glycoprotein activity, and that PKC-inhibitory N-myristoylated PKC- pseudosubstrate synthetic peptides potently and selectively induced uptake of the cytotoxic drugs in the phorbol ester-treated and non-treated colon cancer cells. TPA treatment of the cells did not induce expression of either P-glycoprotein or its message mdr1. In contrast with [14C]Adriamycin and [3H] vincristine uptake, [3H] 5-fluorouracil uptake by the cells was unaffected by TPA and reduced by the PKC-inhibitory peptides. These results indicate that PKC activation can significantly reduce the uptake of multiple cytotoxic drugs by cancer cells independently of P-glycoprotein, and that N-myristoylated PKC- pseudosubstrate peptides potently and selectively induce uptake of multiple cytotoxic drugs in cultured human colon cancer cells by a novel mechanism that does not involve P-glycoprotein and may involve PKC isozyme inhibition. Thus, N-myristoylated PKC- pseudosubstrate peptides may offer a basis for the development of agents that reverse intrinsic drug resistance in human colon cancer. 相似文献
10.
Bouron A 《The European journal of neuroscience》1999,11(12):4446-4450
Cultured hippocampal neurons from neonatal rats were used to investigate the effect of adenosine on the release of glutamate. Spontaneous tetrodotoxin-resistant miniature excitatory postsynaptic currents (mEPSCs) through AMPA receptor channels were recorded by means of the whole-cell patch-clamp technique. Adenosine (50 microM) reversibly reduced the frequency of mEPSCs by approximately 50-60%, but did not change their amplitudes. The protein kinase A inhibitor Rp-cyclic adenosine monophosphate (100-150 microM) did not block the adenosine-dependent reduction of the mEPSC frequency, showing that adenosine is not depressing synaptic transmission via a protein kinase A (PKA)-dependent mechanism. The D1 dopamine agonist SKF-38393 (250 microM), forskolin (5 microM) and 8Br-cAMP (2 mM), known to activate the cAMP/PKA-dependent signalling pathway, all enhanced the mEPSC frequency. A subsequent application of adenosine (50 microM) strongly reduced the potentiation produced by any one of these three drugs. It also reversed protein kinase C (PKC)-dependent stimulation of glutamate release induced by phorbol myristate acetate (100 nM). Taken together, adenosine not only inhibits the spontaneous release of glutamate independently of protein kinases A and C but also reverses the enhancement of exocytosis produced by protein kinases A and C activators. 相似文献