共查询到20条相似文献,搜索用时 15 毫秒
1.
Rainer Voisard Nicola Huber Regine Baur Milorat Susa Oliver Ickrath Anton Both Wolfgang Koenig Vinzenz Hombach 《BMC molecular biology》2001,2(1):7-7
Background
Activation of nuclear factor-κB (NF-κB) is one of the key events in early atherosclerosis and restenosis. We hypothesized that tumor necrosis factor-α (TNF-α) induced and NF-κB mediated expression of intercellular adhesion molecule-1 (ICAM-1) can be inhibited by antisense RelA p65 and NF-κB1 p50 oligonucleotides (RelA p65 and NF-κB1 p50). 相似文献2.
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has been shown to reduce the progression of renal disease
independent of cholesterol-lowering effect, but the mechanism of potential protective effect remains unclear. Here, we investigate
the effect of fluvastatin on activation of nuclear factor-κB (NF-κB) induced by angiotensin II (AngII) in rat kidney tubule
epithelial cells (NRK-52E). Electrophoretic mobility shift assays (EMSA) was used to detect NF-κB activation. Phosphorylation
of cellular p38 mitogen-activated protein kinase (p38MAPK) was determined by western blot analysis. AngII stimulated the DNA-binding
activity of NF-κB and phosphorylation of p38MAPK in cultured NRK-52E cells in a dose-dependent (10−9–10−6 mol/l) manner (P < 0.01). AngII (10−6 mol/l) induced a rapid (5 min) increase of the p38MAPK phosphorylation. NF-κB DNA-binding activity was increased at as early
as 30 min, peaked at 2 h after AngII treatment. This stimulatory effect of AngII on NF-κB was blocked by SB203580 (a specific
inhibitor of p38MAPK). Incubation of cells with fluvastatin significantly inhibited the AngII-induced NF-κB activation in
a dose-dependent (10−7–10−5 mol/l) manner (P < 0.05). Exogenous mevalonate (10−4mol/l) prevented the effect of fluvastatin on NF-κB activation. These results suggest the fluvastatin reduced AngII-induced
NF-κB activation via the p38MAPK pathway in NRK-52E cells. The effect is at least partly due to blocking the biosynthesis
of mevalonate. 相似文献
3.
It has been reported that pretreatment of rats with lipopolysaccharide (LPS) increases myocardial functional recovery in ischemia/reperfusion
(I/R) hearts. However, the mechanisms by which LPS induces cardioprotection against I/R injury have not been fully elucidated.
In this study, we pretreated rats with LPS (1.0 mg/kg) 24 h before they were subjected to I/R injury, and then examined the
roles of heat shock protein-70 (HSP70) and nucleus factor-κB (NF-κB) in LPS-induced cardioprotection. We observed that pretreatment
with low-dose LPS resulted in significantly increased levels of HSP70 in the myocardium, which could dramatically inhibit
NF-κB translocation and reduce degradation of inhibitory κB. Inhibition of NF-κB, in turn, attenuated release of inflammatory
cytokines (tumor necrosis factor-α, interleukin (IL)-1β, and IL-6) and reduced apoptosis of myocardium and infarct area following
I/R injury. Moreover, HSP70 could ameliorate oxidative stress following I/R injury. To further investigate whether increase
of HSP70 might be responsible for protection of the myocardium against I/R injury, we co-administered the HSP70 inhibitor,
quercetin, with LPS before I/R injury. We found that LPS-induced cardioprotection was attenuated by co-administration with
quercetin. Herein, we concluded that increased levels of HSP70 through LPS pretreatment led to inhibition of NF-κB activity
in the myocardium after I/R injury. Our results indicated that LPS-induced cardioprotection was mediated partly through inhibition
of NF-κB via increase of HSP70, and LPS pretreatment could provide a means of reducing myocardial I/R injury. 相似文献
4.
Adriamycin is one of the most effective and useful antineoplastic agents. Acute doxorubicin cardiotoxicity involved cardiomyocyte
apoptosis. In this study, we investigated whether adriamycin induced myocardium apoptosis through activation of nuclear factor
κB in rat. Forty male Wistar rats were randomly divided into five groups: control, ADR 5 mg/kg, ADR 10 mg/kg, ADR 15 mg/kg
group and ADR + PDTC 200 mg/ml group. Myocardial apoptosis was detected by DNA fragmentation assay and TUNEL assay; Location
and distribution of p-IκBα was observed by immunohistochemical assay; Myocardial expression of p-IκBα protein was assessed
by Western blot analysis; Activity of NF-κB was evaluated by Electrophoretic Mobility Shift Assay. The myocardial apoptotic
index, expression of p-IκBα, and binding activity of NF-κB increased significantly in ADR groups in dose-dependent manner.
PDTC as a nonspecific inhibitor of NF-κB protected myocardium from apoptosis by inhibiting NF-κB activation. Adriamycin induces
myocardium apoptosis through activation of nuclear factor κB in rat and NF-κB activation requires IκBα degradation. 相似文献
5.
6.
Effects of glutamine on the nuclear factor-kappaB signaling pathway of murine peritoneal macrophages
Marcelo Macedo Rogero Primavera Borelli Ricardo Ambrósio Fock Maria Carolina Borges Marco Aurélio Ramirez Vinolo Rui Curi Karina Nakajima Amanda Rabello Crisma Aline Domingas Ramos Julio Tirapegui 《Amino acids》2010,39(2):435-441
The aim of this study was to evaluate the effect of glutamine on the expression of proteins involved in the nuclear factor-kappaB
(NF-κB) signaling pathway of murine peritoneal macrophages. Since glutamine is essential for the normal functioning of macrophages,
it was hypothesized that in vitro glutamine supplementation would increase NF-κB activation. Peritoneal macrophages were pretreated
with glutamine (0, 0.6, 2 and 10 mM) before incubation with lipopolysaccharide (LPS), and the effects of glutamine on the
production of tumor necrosis factor-alpha and on the expression and activity of proteins involved in the NF-κB signaling pathway
were studied by an enzyme linked immuno-sorbent assay, Western blotting, and an electrophoretic mobility shift assay. Glutamine
treatment (2 and 10 mM) increased the activation of NF-κB in LPS-stimulated peritoneal macrophages (P < 0.05). In non-stimulated cells, glutamine treatment (2 and 10 mM) significantly reduced IκB-α protein expression (P < 0.05). Glutamine modulates NF-κB signaling pathway by reducing the level of IκB-α, leading to an increase in NF-κB within
the nucleus in peritoneal macrophages. 相似文献
7.
8.
Yoo KY Yoo DY Hwang IK Park JH Lee CH Choi JH Kwon SH Her S Lee YL Won MH 《Neurochemical research》2011,36(12):2417-2426
Innate immune system is very important to modulate the host defense against a large variety of pathogens. Toll-like receptors
(TLRs) play a key role in controlling innate immune response. Among TLRs, TLR4 is a specific receptor for lipopolysaccharide
and associated with the release of pro-inflammatory cytokines. In the present study, we investigated ischemia-related changes
of TLR4 immunoreactivity and its protein level, and nuclear factor κB (NF-κB) p65 immunoreactivity regarding inflammatory
responses in the hippocampal CA1 region after 5 min of transient cerebral ischemia to identify the correlation between transient
ischemia and inflammation. In the sham-operated group, TLR4 immunoreactivity was easily detected in pyramidal neurons of the
hippocampal CA1 region (CA1). TLR4 immunoreactivity in pyramidal neurons was distinctively decreased after ischemia/reperfusion
(I/R); instead, based on double immunofluorescence study, TLR4 immunoreactivity was expressed in non-pyramidal neurons and
astrocytes from 2 days postischemia. In addition, TLR4 protein level was lowest at 1 day postischemia and highest 4 days after
I/R. On the other hand, NF-κB p65 immunoreactivity was not detected in the CA1 of the sham-operated group, and NF-κB p65 immunoreactivity
was not observed until 1 day after I/R. However, NF-κB p65 immunoreactivity began to be expressed in astrocytes at 2 days
postischemia, and the immunoreactivity was strong 4 days postischemia. Our results indicate that TLR4 and NF-κB p65 immunoreactivity
are changed in CA1 pyramidal neurons and newly expressed in astrocytes, not in microglia, in the CA1 region after transient
cerebral ischemia. 相似文献
9.
10.
Background
Pyrin-only protein 2 (POP2) is a small human protein comprised solely of a pyrin domain that inhibits NF-κB p65/RelA and blocks the formation of functional IL-1β processing inflammasomes. Pyrin proteins are abundant in mammals and several, like POP2, have been linked to activation or regulation of inflammatory processes. Because POP2 knockout mice would help probe the biological role of inflammatory regulation, we thus considered whether POP2 is common in the mammalian lineage. 相似文献11.
12.
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
13.
14.
Shu-Yan Li Wen-Ge Sun Yu-Hong Jia Guo-Sheng Wu Guo-Shun An Ju-Hua Ni Hong-Ti Jia 《Biochemistry. Biokhimii?a》2010,75(1):101-110
We demonstrate that activation of nuclear factor κB (NF-κB) in neurons is neuroprotective in response to kainic acid (KA)-induced
excitotoxicity. Combination of Western blotting, immunocytochemistry, and electrophoresis mobility shift assay showed that
KA exposure induced a fast but transient nuclear translocation of the NF-κB p65 subunit and increased DNA-binding activity
of NF-κB in primary cultured cortical neurons. The transient NF-κB activity was associated with upregulation of antiapoptotic
Bcl-xL and XIAP gene products revealed by real-time PCR. Knockdown of p65 decreased neuronal viability and antiapoptotic gene
expression. In addition, we showed that KA-stimulated DNA-binding activity of NF-κB was associated with reactive oxygen species
and calcium signals, using AMPA/KA receptor antagonist, calcium chelator, and antioxidant. These results suggest that the
fast and transient activation of NF-κB initiated by calcium signals is one of the important proximal events in response to
KA-induced excitotoxicity, which has neuroprotective effect against KA-induced apoptosis. 相似文献
15.
16.
17.
Jie Qi Jinsong Zhang Weiguo Feng Xiangdong Luo Changlin Li Zongliang Zhang 《中国科学:生命科学英文版》2000,43(6):578-588
We detected the expression of IL-12 p40/p35 mRNA by semi-quantitative RT-PCR and silver staining, and studied the molecular
interaction between the IL-12 expression and the NF-eB activation induced by LPS and IFN-γ/LPS in murine peritoneal suppressor
macrophages (MPSMs). It was found that IFN-γ strongly enhanced the LPS-induced IL-12 p40 and p35 mRNA expression. Both p40
and p35 mRNA levels were approximately equal. IFN-a also greatly promoted the LPS-induced secretion of IL-12 p70 in MPSMs.
The Proteasome Inhibitor I (PSI) could block the expression of IL-12 p40 and p35 mRNA, and the degradation of IκBα induced
by LPS or LPS/IFN-γ. EMSA showed that LPS could augment the NF-κB binding activity to p40 promoter DNA. However, IFN-γ could
neither enhance the LPS-induced NF-κB activity nor promote the degradation of IκBα. Taken together, the data suggest: (i)
IFN-γ/LPS could strongly induce the expression of IL-12 p40 and p35 mRNA; both the expression levels were equal; this phenomenon
coincided with the high-level secretion of IL-12 p70 induced by IFN-γ/LPS; (ii) NF-κB signal pathway is essential for IFN-γ/LPS
to induce IL-12 mRNA expression; (iii) by blocking the degradation of IκB, the PSI suppresses the IL-12 p40/p35 mRNA expression
induced by LPS and IFN-γ/LPS; (iv) NF-κB signal may not be involved in the mechanism by which IFN-γ enhanced the expression
of the LPS-induced IL-12 p40/p35 mRNA.
The first two authors contributed equally to this work. 相似文献
18.
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
19.
Gang Chen Yufang Qiao Jin Yao Qiqin Jiang Xu Lin Feng Chen Fenghui Lin Miao Lin Lixiang Lin Pengli Zhu 《Molecular biology reports》2011,38(5):3089-3094
To construct a recombinant adenovirus vector expressing a RNAi for the Nuclear Factor kappa B (NF-κB)/p65 gene and use it
to explore the role of the NF-κB pathway on the regulation of proliferation and apoptosis of vascular endothelial cells. A
recombinant adenovirus containing a RNAi cassette targeting the p65 gene was constructed, and its silencing effect on p65
was detected by Western blot analysis in ECV304 cells. Expression of the p65 protein in ECV304 cells was efficiently down-regulated
by the RNAi adenovirus for more than 6 days. ECV304 cells proliferation and apoptosis were measured using the MTT assay and
flow cytometry, respectively. Blocking the NF-κB pathway with the RNAi adenovirus substantially decreased the proliferation
of ECV304 cells, but only slightly affected cell apoptosis. We used a NF-κB/p65-targeting RNAi adenovirus to demonstrate the
role of the NF-κB pathway in the regulation of ECV304 cell proliferation. This adenovirus may serve as an important tool to
study the NF-κB pathway. 相似文献
20.
High levels of homocysteine promote cell damage mainly through induction of oxidative stress, endoplasmic reticulum (ER) stress,
and activation of pro-inflammatory factors. The effects of homocysteine were here examined in the continuously dividing neuroblastoma
cell line Neuro2a. Cell treatment with homocysteine (100–500 μM) for 4 h increased ROS production while reducing cell viability
in a dose-dependent manner. Cell exposure to 250 μM homocysteine was able to induce transglutaminase 2 up-regulation and increased
in situ transglutaminase activity. These effects were prevented by the incubation with the transglutaminase activity inhibitor
cystamine. Homocysteine also induced NF-κB activation that seemed associated with transglutaminase 2 up-regulation since the
specific NF-κB inhibition by SN50 was able to reduce transglutaminase expression and activity levels. In the light of these
observations, it may be postulated that TG2 up-regulation is involved in cell response to homocysteine-induced stress, in
which NF-κB activation plays also a pivotal role. 相似文献