共查询到20条相似文献,搜索用时 15 毫秒
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Nakaizumi A Horie T Kida T Kurimoto T Sugiyama T Ikeda T Oku H 《Cellular and molecular neurobiology》2012,32(1):95-106
Modulation of enzyme activity through nitrosylation has recently been identified as a new physiological activity of nitric
oxide (NO). We hypothesized that NO enhances the TNF-α-induced death of retinal neurons through a suppression of nuclear factor-κB
(NF-κB) by nitrosylation. In this study, cells from the RGC-5 line were exposed to different concentrations (2.0, 10, and
50 ng/ml) of TNF-α, and the degree of TNF-α-induced cell death was determined by the WST-8 assay and by flow cytometric measurements
of the externalization of phosphatidylserine. The effects of etanercept, a soluble TNFR-Fc fusion protein, and S-nitroso-N-penicillamine (SNAP), an NO donor, on the toxicity were determined. Experiments were also performed to determine whether
nitric oxide synthase (NOS) was associated with the toxicity of TNF-α. The activation of NF-κB was determined by the detection
of the p65 subunit in the nuclear extracts. Our results showed that exposure of RGC-5 cells to different concentrations of
TNF-α significantly decreased the number of living cells in a dose-dependent way. The death was partially due to apoptosis
with an externalization of phosphatidylserine, and the death was suppressed by etanercept. Exposure to TNF-α increased the
activation of NF-κB and the expression of iNOS. Although NF-κB inhibitors suppressed the increase of iNOS, they also potentiated
the TNF-α-induced death. Both L-NAME and aminoguanidine, both NOS inhibitors, rescued the cells from death. In contrast, addition
of SNAP caused nitrosylation of the inhibitory κB kinase, and suppressed the NF-κB activation and potentiated the TNF-α-induced
neurotoxicity. These results indicate that NO potentiates the neurotoxicity of TNF-α by suppressing NF-κB. 相似文献
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Morchella conica is a species of rare edible mushroom whose multiple medicinal functions have been proven. However, reports barely mention
the mechanisms of these functions. In this study, the effects of two polysaccharides from M. conica (PMCs) on nitric oxide (NO) production in lipopolysaccharide (LPS)-treated macrophages were investigated. The results showed
that 50–200 μg/ml of the extracellular polysaccharide (EPMC) and 25–200 μg/ml of the intracellular polysaccharide (IPMC) significantly
inhibited NO production. Accordingly, the signal mechanisms were also explored. It was found that 100 μg/ml of EPMC and 25 μg/ml
of IPMC could efficiently down-regulate the inducible nitric oxide synthase (iNOS) expression and nuclear factor-κB (NF-κB)
DNA-binding activity and up-regulate heme oxygenase 1 (HO-1) expression. Moreover, by using a HO-1 inhibitor NaPP to treat
the cells, the PMC-inhibited NO production and iNOS expression, rather than NF-κB activation, were released partially, indicating
that HO-1 probably medicates the inhibition of PMCs on iNOS and NO. Besides, EPMC also significantly suppressed the phosphorylation
of p38 mitogen-activated protein kinase (p38), c-jun N-terminal kinase, mitogen-activated protein kinase kinase 4, and expression
of NF-κB inducing kinase, while IPMC seemed to show no regular effect on p38. In conclusion, PMCs inhibited NO production
in LPS-induced macrophages through regulating a series of signal pathways, suggesting that PMCs play a potential role on immunomodulation
and treating related diseases. 相似文献
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Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through
its anti-oxidative effect and modulation of NF-kappa B activation 总被引:15,自引:0,他引:15
Wang YH Wang WY Chang CC Liou KT Sung YJ Liao JF Chen CF Chang S Hou YC Chou YC Shen YC 《Journal of biomedical science》2006,13(1):127-141
Summary Infarction in adult rat brain was induced by middle cerebral arterial occlusion (MCAO) followed by reperfusion to examine
whether taxifolin could reduce cerebral ischemic reperfusion (CI/R) injury. Taxifolin administration (0.1 and 1.0 μg/kg, i.v.)
60 min after MCAO ameliorated infarction (by 42%±7% and 62%±6%, respectively), which was accompanied by a dramatic reduction
in malondialdehyde and nitrotyrosine adduct formation, two markers for oxidative tissue damage. Overproduction of reactive
oxygen species (ROS) and nitric oxide (NO) via oxidative enzymes (e.g., COX-2 and iNOS) was responsible for this oxidative damage. Taxifolin inhibited leukocyte infiltration,
and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors
involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte
infiltration. ROS, generated by leukocytes and microglial cells, activated nuclear factor-kappa B (NF-κB) that in turn signaled
up-regulation of inflammatory proteins. NF-κB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited
by taxifolin. Production of both ROS and NO by leukocytes and microglial cells was significantly antagonized by taxifolin.
These data suggest that amelioration of CI/R injury by taxifolin may be attributed to its anti-oxidative effect, which in
turn modulates NF-κB activation that mediates CI/R injury.
Yea-Hwey Wang, Wen-Yen Wang, Chia-Che Chang, and Kuo-Tong Liou contributed equally to this work. 相似文献
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Vaysberg M Hatton O Lambert SL Snow AL Wong B Krams SM Martinez OM 《The Journal of biological chemistry》2008,283(52):36573-36585
Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is a proven oncogene that is essential for transformation of human B cells by the virus. LMP1 induces constitutive activation of several signal transduction pathways involving nuclear factor kappaB, phosphatidylinositol 3-kinase/Akt, and the mitogen-activated protein kinases (MAPK) p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (Erk). Sequencing of LMP1 isolated from a panel of EBV+ B cell lymphomas identified three different variants of LMP1, each distinct from the B95.8 prototype isoform. All tumor variants of LMP1 as well as the B95.8 LMP1 isoform were able to induce rapid p38 phosphorylation as well as Akt and JNK activation. Additionally all variants showed similar ability to activate nuclear factor kappaB. In contrast, only tumor-derived LMP1 variants induced prolonged Erk activation and c-Fos expression. Sequence analysis revealed only two amino acids, 212 and 366, shared by the tumor variants but distinct from B95.8. Point mutation of either amino acids 212 (glycine to serine) or 366 (serine to threonine) from the B95.8 isoform to the tumor variant version of LMP1 was sufficient for gain of function characterized by sustained activation of Erk and subsequent c-Fos induction and binding to the AP1 site. Our results indicate that the enhanced ability of tumor-derived LMP1 to induce and stabilize the c-Fos oncogene can be localized to two amino acids in the C terminus of LMP1. 相似文献
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Background
Chronic lung disease (CLD) of prematurity is a major problem of neonatal care. Bacterial infection and inflammatory response have been thought to play an important role in the development of CLD and steroids have been given, with some benefit, to neonates with this disease. In the present study, we assessed the ability of lipopolysaccharide (LPS) to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS) and activate nuclear factor-κB (NF-κB) in vitro. In addition, we investigated the impact of dexamethasone and budesonide on these processes. 相似文献11.
The 30-Base-Pair Deletion in Chinese Variants of the Epstein-Barr Virus LMP1 Gene Is Not the Major Effector of Functional Differences between Variant LMP1 Genes in Human Lymphocytes 总被引:4,自引:3,他引:4 下载免费PDF全文
Rowena J. Johnson Maria Stack Sheila A. Hazlewood Matthew Jones Colin G. Blackmore Li-Fu Hu Martin Rowe 《Journal of virology》1998,72(5):4038-4048
One group of sequence variants of Epstein-Barr virus is characterized by a 10-amino-acid deletion within the CTAR-2 functional domain of the latent membrane protein, LMP1. A role for this deletion in enhancing the tumorigenicity of the viral oncogene in rodent fibroblasts was recently demonstrated. We examined the effect of this deletion upon LMP1 function in four human lymphoid cell lines by using three natural variants of LMP1: the prototype B95.8 gene and the CAO and AG876 genes, both of which have codons 343 to 352 of the B95.8-LMP1 deleted. These experiments revealed that LMP1-mediated upregulation of CD40 and CD54 was markedly impaired (by 60 to 90%) with CAO-LMP1 compared with B95.8-LMP1. In contrast, the function of AG876-LMP1 was indistinguishable from that of B95.8-LMP1 in two lines and was only slightly impaired in the other two lines. Activation of NF-κB by CAO-LMP1 was not impaired in any of the lines; rather, activation of an NF-κB reporter by CAO-LMP1 was consistently about twofold greater than the activation with B95.8- or AG876-LMP1. Therefore, while the CAO-LMP1 is functionally distinct from the prototype B95.8-LMP1 in human lymphocytes, the 10-amino-acid deletion appears not to be directly responsible. This conclusion was confirmed by using a B95.8-LMP1 mutant with codons 343 to 352 deleted and chimerae of CAO- and B95.8-LMP1 in which the CTAR-2 domains of these genes were exchanged. Sequences outside the CTAR-2 domain were implicated in the distinct functional characteristics of CAO-LMP1 in human lymphoid cells. 相似文献
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Sun CS Wu KT Lee HH Uen YH Tian YF Tzeng CC Wang AH Cheng CJ Tsai SL 《Journal of biomedical science》2008,15(5):633-643
The link of proto-oncogenic protein Wnt-1 production with NF-κB activation has been functionally demonstrated in PC12 cells, a rat pheochromocytoma cell line of neural
crest lineage, while it is not yet verified in human cells. The link can be indirectly supported in our previous report that
functional proteomics identifies enhanced expression of NF-κB-associated Wnt-1 production in human hepatocellular carcinoma tissues. This study aimed to further validate this link in human cells using
anti-sense strategy. The effects of sequence-specific anti-sense morpholino oligonucleotides (ONs) targeting against pre-mRNA
sequences of human p50 and p65 subunits of NF-κB as well as Wnt-1 genes were investigated. It revealed that all the three morpholino ONs inhibited NF-κB activation in human hepatoblastoma
cell line HepG2 cells along with decreased Wnt-1 production. Chromatin immunoprecipitation assay ascertained the direct binding of NF-κB-p50 to the Wnt-1 promoter. Additionally, anti-P50 and anti-P65 morpholino ONs also repressed the phosphorylation of Iκ Bα which temporarily
correlated with the inhibition of NF-κB activation accompanied by decreased Wnt-1 production by HepG2 cells. In summary, NF-κB activation is critically involved in the production of Wnt-1 by HepG2 cells. These results may have important oncology implications in treating patients with NF-κB-associated Wnt-1-producing cancers.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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Salsolinol, an endogenous neurotoxin, is known to be involved in the pathogenesis of Parkinson’s disease (PD). In the present
study, we have investigated the effects of salsolinol on the activation of two different signaling pathways that involve c-Jun
N-terminal kinase (JNK), and nuclear factor-κB, (NF-κB) in human dopaminergic neuroblastoma SH-SY5Y cells. Salsolinol treatment
caused upregulation in the levels of c-Jun and phosphorylated c-Jun. It also caused degradation of IκBα and translocated the
active NF-κB into the nucleus. The binding activity of NF-κB to DNA was enhanced by salsolinol in a concentration dependent
manner. Furthermore, salsolinol decreased the levels of the anti-apoptotic protein Bcl-2, and increased pro-apoptotic protein
Bax, while enhancing the release of cytochrome-c from mitochondria. Mitochondrial complex-I activity was significantly decreased and reactive oxygen species (ROS) were increased
in salsolinol treated cells. These results partly suggest that salsolinol-induced JNK and NF-κB signaling pathways may be
involved in induction of apoptosis in human dopaminergic neurons, as seen in Parkinson’s disease. 相似文献
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We have demonstrated that the expressions of small molecular weight G-protein, H-Ras, and its effector protein, Raf-1, are
increased in the retina in diabetes, and the specific inhibitors of Ras function inhibit glucose-induced apoptosis of retinal
capillary cells. This study is to examine the contributory roles for H-Ras in glucose-induced apoptosis of retinal endothelial
cells by genetic manipulation of functionally active H-Ras levels. Bovine retinal endothelial cells were transfected with
the plasmids of either wild type (WT), constitutively active (V12) or dominant-negative (N17) H-Ras. Glucose-induced increase
in apoptosis, nitric oxide (NO) levels and activation of NF-κB and caspase-3 were determined in these genetically manipulated
cells. Exposure of bovine retinal endothelial cells to 20 mM glucose significantly increased H-Ras activation as determined
by Raf-1 binding assay. Overexpression of V12 in the endothelial cells further increased their glucose-induced apoptosis by
40%, NO levels by about 50%, and activated NF-κB and caspase-3 by about 30–40% compared to the untransfected cells incubated
in 20 mM glucose. In contrast, overexpression of the inactive mutant, N17, inhibited glucose-mediated increases in apoptotic
cell death, NO levels and NF-κB and caspase-3 activation; the values were significantly different (p < 0.02) compared to those obtained from the untransfected cells incubated under similar conditions. Our findings demonstrate
that H-Ras activation is important in the activation of the specific signaling events leading to the accelerated retinal capillary
cell apoptosis in hyperglycemic conditions, suggesting the possible use of H-Ras inhibitors to inhibit the pathogenesis of
diabetic retinopathy. 相似文献
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Neuroprotective Effects of (-)-Epigallocatechin-3-gallate in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis 总被引:3,自引:0,他引:3
The purpose of this study is to evaluate neuroprotective effects of (-)-Epigallocatechin-3-gallate (EGCG) in a transgenic mouse model of Amyotrophic lateral sclerosis (ALS). SOD1-G93A transgenic mice and wild-type mice were randomly divided into EGCG-treated groups (10 mg/kg, p.o) and vehicle-treated control groups. Rotarod measurement was performed to assess the motor function of mice starting at the age of 70 days. Nissl staining to examine the number of motor neurons and CD11b immunohistochemical staining to evaluate activation of microglia in the lumbar spinal cords were conducted at the age of 120 days. In addition, for further observation of regulation of cell signaling pathways by EGCG, we used immunohistochemical analysis for nuclear factor kappa B (NF-κB) and cleaved caspase-3 as well as western blot analysis to determine the expression of nitric oxide synthase (iNOS) and NF-κB in the spinal cord. This study demonstrated that oral administration of EGCG beginning from a pre-symptomatic stage significantly delayed the onset of disease, and extended life span. Furthermore, EGCG-treated transgenic mice showed increased number of motor neurons, diminished microglial activation, reduced immunohistochemical reaction of NF-κB and cleaved caspase-3 as well as reduced protein level of iNOS and NF-κB in the spinal cords. In conclusion, this study provides further evidences that EGCG has multifunctional therapeutic effects in the mouse model of ALS. 相似文献
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Gypenoside XLIX isolated from Gynostemma pentaphyllum inhibits nuclear factor-kappaB activation via a PPAR-alpha-dependent pathway 总被引:2,自引:0,他引:2
Huang TH Li Y Razmovski-Naumovski V Tran VH Li GQ Duke CC Roufogalis BD 《Journal of biomedical science》2006,13(4):535-548
Summary Nuclear factor (NF)-κB is important in the generation of inflammation. Besides regulating lipid metabolism, peroxisome proliferator-activated receptor (PPAR)-α activators also reduce NF-κB activation to terminate activation of inflammatory pathways. Gynostemma pentaphyllum (GP) has been used to treat various inflammatory diseases and hyperlipidemia. Here, we demonstrate that GP extract and one of its main components, Gypenoside XLIX (Gyp-XLIX) inhibited LPS-induced NF-κB activation in murine macrophages. Furthermore, Gyp-XLIX restored the LPS- and TNF-α-induced decrease in cytosolic I-κBα protein expression and inhibited the translocation of NF-κB(p65) to the nucleus in THP-1 monocyte and HUVEC cells. The inhibition of LPS- and TNF-α-induced NF-κB luciferase activity in macrophages was abolished by MK-886, a selective PPAR-α antagonist. GP extract and Gyp-XLIX (EC50: 10.1 μM) enhanced PPAR-α luciferase activity in HEK293 cells transfected with the tK-PPREx3-Luc reporter plasmid and expression vectors for PPAR-α. Additionally, Gyp-XLIX specifically enhanced PPAR-α mRNA and protein expression in THP-1-derived macrophage cells. The selectivity of Gyp-XLIX for PPAR-α was demonstrated by the activation of only PPAR-α in HEK293 cells transfected with expression vectors for PPAR-α, PPAR-β/δ or PPAR-γ1 plasmids and in THP-1-derived macrophage naturally expressing all three PPAR isoforms. The present study demonstrates that Gyp-XLIX, a naturally occurring gynosaponin, inhibits NF-κB activation via a PPAR-α-dependent pathway.Tom Hsun-Wei Huang and Yuhao Li contributed equally. 相似文献