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1.
目的通过胰岛素和磷脂酰肌醇-3激酶(P13K)抑制剂渥曼青霉素(wortmannin)对P13K/丝氨酸苏氨酸蛋白激酶(P13K/Akt)信号通路的激活和抑制作用,观察P13K/Akt信号通路对海马神经元β-淀粉样前体蛋白裂解酶1(BACEl)mRNA水平表达的影响。方法20只sD大鼠随机分为空白对照组、假手术组、胰岛素组和渥曼青霉素组,海马立体定向注射胰岛素和P13K抑制剂渥曼青霉素。逆转录一聚合酶链反应(RT-PCR)检测P13K/Akt信号传导下游蛋白Akt以及BACEImRNA水平。结果注射胰岛素的海马P13K信号通路下游信号分子:AktmRNA表达上调(分别较空白和阴性对照组P=0.047,P=0.002),而BACElmRNA表达下调(分别较空白和阴性对照组P=0.004,P=0.01)。渥曼青霉素组的P13K下游信号分子AktmRNA表达明显被抑制(分别较空白和阴性对照组P=0.002,P=0.039),同时BACEImRNA的表达较对照组上调(分别较空白和阴性对照组P=0.039,P=0.018)。结论胰岛素信号通路P13K/AM可以调节BACEl的转录水平参与阿尔茨海默病的发病机制。 相似文献
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Gasperi V Fezza F Pasquariello N Bari M Oddi S Agrò AF Maccarrone M 《Cellular and molecular life sciences : CMLS》2007,64(2):219-229
The molecular basis for the control of energy balance by the endocannabinoid anandamide (AEA) is still unclear. Here, we show
that murine 3T3-L1 fibroblasts have the machinery to bind, synthesize and degrade AEA, and that their differentiation into
adipocytes increases by approximately twofold the binding efficiency of cannabinoid receptors (CBR), and by approximately
twofold and approximately threefold, respectively, the catalytic efficiency of the AEA transporter and AEA hydrolase. In contrast,
the activity of the AEA synthetase and the binding efficiency of vanilloid receptor were not affected by the differentiation
process. In addition, we demonstrate that AEA increases by approximately twofold insulin-stimulated glucose uptake in differentiated
adipocytes, according to a CB1R-dependent mechanism that involves nitric oxide synthase, but not lipoxygenase or cyclooxygenase.
We also show that AEA binding to peroxisome proliferator-activated receptor-γ, known to induce differentiation of 3T3-L1 fibroblasts
into adipocytes, is not involved in the stimulation of glucose uptake.
Received 11 October 2006; received after revision 9 November 2006; accepted 28 November 2006
V.Gasperi and F. Fezza equally contributed to the study. 相似文献
3.
Kim SH Juhnn YS Kang S Park SW Sung MW Bang YJ Song YS 《Cellular and molecular life sciences : CMLS》2006,63(7-8):930-938
The E5 oncoprotein of human papillomavirus (HPV) 16 plays an important role in early cervical carcinogenesis. Vascular endothelial
growth factor (VEGF) plays a central role in switching on the angiogenic phenotype during early cervical carcinogenesis. However,
the relationship between E5 and VEGF has not previously been examined. To clarify the regulatory role of E5 in VEGF expression,
we transferred the E5 gene into various cell types. E5 increased VEGF expression. The addition of epidermal growth factor
receptor (EGFR) inhibitor significantly suppressed VEGF expression, demonstrating that E5 stimulates VEGF expression through
the activation of EGFR. E5-mediated EGFR activation was accompanied by phosphorylation of Akt and ERK1/2, which are also involved
in VEGF expression. Furthermore, the mRNA stability of VEGF was not affected by E5, but VEGF promoter activity could be modulated
by inhibitors of the EGFR, MEK-ERK1/2 and PI3K/Akt pathways in E5-expressing cells. Collectively, these novel results suggest
that HPV 16 E5 increases VEGF expression by activating EGFR, MEK/ERK1/2 and PI3K/Akt.
Received 23 November 2005; received after revision 10 January 2006; accepted 9 February 2006 相似文献
4.
Emodin inhibits tumor cell migration through suppression of the phosphatidylinositol 3-kinase-Cdc42/Rac1 pathway 总被引:6,自引:0,他引:6
Enhanced cell migration is one of the underlying mechanisms in cancer invasion and metastasis. Therefore, inhibition of cell migration is considered to be an effective strategy for prevention of cancer metastasis. We found that emodin (3-methyl-1,6,8-trihydroxyanthraquinone), an active component from the rhizome of Rheum palmatum, significantly inhibited epidermal growth factor (EGF)- induced migration in various human cancer cell lines. In the search for the underlying molecular mechanisms, we demonstrated that phosphatidylinositol 3-kinase (PI3K) serves as the molecular target for emodin. In addition, emodin markedly suppressed EGF-induced activation of Cdc42 and Rac1 and the corresponding cytoskeleton changes. Moreover, emodin, but not LY294002, was able to block cell migration in cells transfected with constitutively active (CA)-Cdc42 and CA-Rac1 by interference with the formation of Cdc42/Rac1 and the p21-activated kinase complex. Taken together, data from this study suggest that emodin inhibits human cancer cell migration by suppressing the PI3K-Cdc42/Rac1 signaling pathway.Received 7 February 2005; received after revision 11 March 2005; accepted 18 March 2005 相似文献
5.
Liu ZM Chen GG Vlantis AC Tse GM Shum CK van Hasselt CA 《Cellular and molecular life sciences : CMLS》2007,64(11):1428-1436
The molecular mechanism responsible for cadmium-induced cell death in thyroid cancer cells (FRO) is unknown. We demonstrated
that apoptosis of FRO cells induced by cadmium was concentration and time dependent. Cadmium caused the rapid elevation of
intracellular calcium and induced phosphorylation of Akt, p53, JNK, ERK and p38. Inhibition of PI3K/Akt attenuated the cadmium-induced
apoptosis, but the inhibition of JNK inhibitor, ERK or p38 aggravated it, indicating that activation of PI3K/Akt was a pro-apoptosis
signal in response to cadmium treatment, whereas the activation of stress-activated protein kinase JNK, ERK and p38 functioned
as survival signals to counteract the cadmium-induced apoptosis. Buffering of the calcium response attenuated mitochondrial
impairment, recovered the cadmium-activated Akt, p53, JNK, ERK and p38, and subsequently blocked the apoptosis. These results
suggested that apoptosis induced by cadmium in FRO cells was initiated by the rapid elevation of intracellular calcium, followed
by calcium-mediated activation of PI3K/Akt and mitochondrial impairment.
Received 28 February 2007; received after revision 2 April 2007; accepted 23 April 2007 相似文献
6.
Tang M Zhong M Shang Y Lin H Deng J Jiang H Lu H Zhang Y Zhang W 《Cellular and molecular life sciences : CMLS》2008,65(18):2924-2932
Advanced glycation end products (AGEs) play an important role in collagen deposition in diabetic cardiomyopathy. TRB3, a mammalian
homolog of Drosophila tribbles, functions to increase glucose intolerance and regulates cell proliferation. We demonstrated
that AGEs induce collagen type I expression but inhibit collagen type III expression, accompanied by increased TRB3 expression.
Furthermore, the collagen type I induced byAGEs was down-regulated after inhibition of ERK and p38-MAPK, the collagen type
III reduced by AGEs was up-regulated after inhibition of ERK. The expression of collagen types I and III regulated by AGEs
through MAPK was partly reversed after treatment with TRB3 siRNA. It suggests that the TRB3/MAPK signaling pathway participates
in the regulation of collagen types I and III by AGEs and may provide new therapeutic strategies for diabetic cardiomyopathy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 08 May 2008; received after revision 25 June 2008; accepted 22 July 2008
M. Tang, M. Zhong: These two authors contributed equally to this work. 相似文献
7.
A. Velasco Martín J. M. Arévalo Alonso M. de Armijo Valenzuela 《Cellular and molecular life sciences : CMLS》1972,28(8):934-934
Resumen La mecloqualona inhibe in vitro, la respiración de cortes y homogenizados de cerebro, incrementando el consumo de glucosa; este último efecto no se produce cuando al medio de incubación se añaden 100 mM de potasio. 相似文献
8.
Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt and mTOR signaling pathways 总被引:1,自引:0,他引:1
M. Y. Lee S. H. Lee J. H. Park H. J. Han 《Cellular and molecular life sciences : CMLS》2009,66(8):1467-1478
Galectins have the potential to provide a promising alternative for unveiling the complexity of embryonic stem (ES) cell self-renewal,
although the mechanism by which galectins maintain ES cell self-renewal has yet to be identified. Galectin-1 increased [3H]-thymidine incorporation as well as cyclin expression and decreased p27kip1 expression. Src and caveolin-1 phosphorylation was increased by galectin-1, and phospho-caveolin-1 was inhibited by PP2.
In addition, inhibition of caveolin-1 by small interfering RNA and methyl-β-cyclodextrin (Mβ-CD) decreased galectin-1-induced
cyclin expression and [3H]-thymidine incorporation. Galectin-1 caused Akt and mTOR phosphorylation, which is involved in cyclin expression. Galectin-1-induced
phospho-Akt and -mTOR was inhibited by PP2, ERas siRNA, caveolin-1 siRNA and Mβ-CD. Furthermore, mTOR phosphorylation was
decreased by LY294002 and Akt inhibitor. Galectin-1-induced increase in cyclin expression and decrease in p27kip1 was blocked by Akt inhibitor and rapamycin. In conclusion, galectin-1 increased DNA synthesis in mouse ES cells via Src,
caveolin-1 Akt, and mTOR signaling pathways.
Received 30 October 2008; received after revision 18 February 2009; accepted 24 February 2009 相似文献
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Zusammenfassung In der Kultur embryonalen Hühnchengewebes kommt es unter Einfluss nichtsteroider Antiphlogistica (Aspirin, Indomethacin, Mefenamicsäure) zu einer Steigerung des Glukoseverbrauchs bei gleichzeitiger Vermehrung der Milchsäureerzeugung. Der Milchsäureverbrauch verläuft in zwei Phasen, wobei der erste Gipfel bei geringsten Konzentrationen des Arzneimittels.auftritt. 相似文献
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Jiong-Yu Hu Zhi-Gang Chu Jian Han Yong-ming Dang Hong Yan Qiong Zhang Guang-ping Liang Yue-Sheng Huang 《Cellular and molecular life sciences : CMLS》2010,67(2):321-333
In both cardiomyocytes and HeLa cells, hypoxia (1% O2) quickly leads to microtubule disruption, but little is known about how microtubule dynamics change during the early stages
of hypoxia. We demonstrate that microtubule associated protein 4 (MAP4) phosphorylation increases while oncoprotein 18/stathmin
(Op18) phosphorylation decreases after hypoxia, but their protein levels do not change. p38/MAPK activity increases quickly
after hypoxia concomitant with MAP4 phosphorylation, and the activated p38/MAPK signaling leads to MAP4 phosphorylation and
to Op18 dephosphorylation, both of which induce microtubule disruption. We confirmed the interaction between phospho-p38 and
MAP4 using immunoprecipitation and found that SB203580, a p38/MAPK inhibitor, increases and MKK6(Glu) overexpression decreases
hypoxic cell viability. Our results demonstrate that hypoxia induces microtubule depolymerization and decreased cell viability
via the activation of the p38/MAPK signaling pathway and changes the phosphorylation levels of its downstream effectors, MAP4
and Op18. 相似文献
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Massimiliano G. Bianchi Donatella Bardelli Martina Chiu Ovidio Bussolati 《Cellular and molecular life sciences : CMLS》2014,71(11):2001-2015
Excitatory amino acid transporters (EAATs) are high-affinity Na+-dependent carriers of major importance in maintaining glutamate homeostasis in the central nervous system. EAAT3, the human counterpart of the rodent excitatory amino acid carrier 1 (EAAC1), is encoded by the SLC1A1 gene. EAAT3/EAAC1 is ubiquitously expressed in the brain, mostly in neurons but also in other cell types, such as oligodendrocyte precursors. While most of the glutamate released in the synapses is taken up by the “glial-type” EAATs, EAAT2 (GLT-1 in rodents) and EAAT1 (GLAST), the functional role of EAAT3/EAAC1 is related to the subtle regulation of glutamatergic transmission. Moreover, because it can also transport cysteine, EAAT3/EAAC1 is believed to be important for the synthesis of intracellular glutathione and subsequent protection from oxidative stress. In contrast to other EAATs, EAAT3/EAAC1 is mostly intracellular, and several mechanisms have been described for the rapid regulation of the membrane trafficking of the transporter. Moreover, the carrier interacts with several proteins, and this interaction modulates transport activity. Much less is known about the slow regulatory mechanisms acting on the expression of the transporter, although several recent reports have identified changes in EAAT3/EAAC1 protein level and activity related to modulation of its expression at the gene level. Moreover, EAAT3/EAAC1 expression is altered in pathological conditions, such as hypoxia/ischemia, multiple sclerosis, schizophrenia, and epilepsy. This review summarizes these results and provides an overall picture of changes in EAAT3/EAAC1 expression in health and disease. 相似文献
13.
Zusammenfassung Ein direkter Zusammenhang zwischen der crsten Phase (K1) und der zweiten Phase (K2) der fraktionellen Senkung des Bromsulphthaleinspiegels hat sich an von hepatoxischcn Krankheiten befallenen Kühen und Schafen erwiesen. Es ist anzunehmen, dass die K2-Werte empfindlichere Nachweise der Lebertätigkeit in diesen Tieren aufweisen als die K1-Werte. 相似文献
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A. Benderly R. T. Coutts A. L. C. Mak G. B. Baker 《Cellular and molecular life sciences : CMLS》1981,37(3):294-295
Summary The (+)- and (–)-isomers of the monofluorinated amphetamine 2-amino-3-fluoro-1-phenylpropane were prepared and compared for their ability to stimulate release and to inhibit reuptake of radiolabelled dopamine from rat striatal tissue in vitro. The (+)-isomer was much stronger than the (–)-isomer in both cases.Financial support for this project was supplied by the Medical Research Council of Canada, the Alberta Mental Health Research Fund and the Special Services and Research Committee, University of Alberta Hospital.Acknowledgments. Skilled technical assistance was provided by Ms L. Hiob. The authors also wish to thank Dr W.G. Dewhurst, Department of Psychiatry, and Dr D.F. LeGatt, for their advice and comments. 相似文献
16.
J. Zídková V. Větvička P. Rossmann V. Dlabač J. Stránsky 《Cellular and molecular life sciences : CMLS》1984,40(9):975-977
Summary The third component of the pig complement system (C3) was isolated in hemolytically active form and characterized. The C3 component is a -globulin with the molecular weight of 191,000 and is composed of 2 non-identical polypeptide chains of Mt 112,000 and 74,000. The isolated C3 can be used for the detection of the C3b receptor on the membranes of heterologous peritoneal macrophages. 相似文献
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Phosphatidylinositol 3-kinase (PI3-kinase) activity has been implicated in regulating cell cycle progression at distinct points
in the cell cycle by preventing cell cycle arrest or apoptosis. In this study, the role of PI3-kinase activity during the
entire G1 phase of the ongoing cell cycle was studied in Chinese hamster ovary (CHO) cells synchronized by mitotic shake-off.
We show that inhibition of PI3-kinase activity during and 2 h after mitosis inhibited cell cycle progression into S phase.
In the presence of the PI3-kinase inhibitor wortmannin or LY294002, cells were arrested during early G1 phase, leading to
the expression of the cleaved caspase-3, a central mediator of apoptosis. These results demonstrate that PI3-kinase activity
is required for progression through the M/G1 phase. In the absence of PI3-kinase activity, cells are induced for apoptosis
in this particular phase of the cell cycle.
Received 7 September 2005; received after revision 26 October 2005; accepted 11 November 2005 相似文献