共查询到20条相似文献,搜索用时 31 毫秒
1.
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
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.
4.
Shieh JM Cheng TH Shi MD Wu PF Chen Y Ko SC Shih YW 《Cell biochemistry and biophysics》2011,60(3):297-310
α-Tomatine, isolated from Lycopersicon esculentum Linn., is a naturally occurring steroidal glycoalkaloid in immature green tomatoes. Some reports demonstrated that α-tomatine
had various anticarcinogenic properties. The purpose of this study is to investigate the anti-metastatic effect of α-tomatine
in NCI-H460 human non-small cell lung cancer cells. First, the results showed that α-tomatine significantly suppressed the
abilities of the adhesion, invasion, and migration of NCI-H460 cells under non-cytotoxic concentrations. Molecular data also
showed α-tomatine could inhibit the activation of focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K)/Akt
signal involve in the downregulation the enzyme activities, protein and messenger RNA levels of matrix metalloproteinase-7
(MMP-7). Next, α-tomatine also strongly inhibited the degradation of inhibitor of kappaBα (IκBα) and the nuclear levels of
nuclear factor kappa B (NF-κB). Also, a dose-dependent inhibition on the binding ability of NF-κB by α-tomatine treatment
was further observed. Furthermore, α-tomatine significantly decreased the levels of phospho-Akt and MMP-7 in Akt1-cDNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. Presented results indicated
α-tomatine might be further application for treating cancer metastasis. 相似文献
5.
6.
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7.
Involved in the ongoing debate is the speculation that aluminium is somehow toxic for neurons. Glial cells cope up to protect
neurons from this toxic insult by maintaining the glutathione homeostasis. Of late newer and newer roles of glial cells have
been depicted. The present work looks into the other regulatory mechanisms that show the glial cells response to pro-oxidant
effects of aluminium exposure. In the present investigation we have evaluated the inflammatory responses of the glial cells
as well as HSP70-induction during aluminium exposure. Further, the protective role of curcumin is also evaluated. Aluminium
was administered by oral gavage at a dose level of 100 mg/kg b.wt/day for a period of 8 weeks. Curcumin was administered i.p.
at a dose of 50 mg/kg b.wt./day on alternate days. Enhanced gene and protein expression of HSP70 in the glial fractions of
the aluminium exposed animals as compared to the corresponding neuronal population. Aluminium exposure resulted in a significant
increase in the NF-κB and TNF-α expression suggesting inflammatory responses. In the conjunctive treatment group of aluminium
and curcumin exposure marked reduction in the gene and protein expression of NF-κB and TNF-α was observed. This was further
reflected in histopathological studies showing no evidence of inflammation in conjunctive group as compared to aluminium treatment.
From the present study, it can be concluded that curcumin has a potential anti-inflammatory action and can be exploited in
other toxicological conditions also. 相似文献
8.
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
9.
10.
11.
Kyoko Wakamatsu Toshihiro Nanki Nobuyuki Miyasaka Kazuo Umezawa Tetsuo Kubota 《Arthritis research & therapy》2005,7(6):R1348
A small cell-permeable compound, dehydroxymethylepoxyquinomicin (DHMEQ), does not inhibit phosphorylation and degradation
of IκB (inhibitor of nuclear factor-κB [NF-κB]) but selectively inhibits nuclear translocation of activated NF-κB. This study
aimed to demonstrate the antiarthritic effect of this novel inhibitor of the NF-κB pathway in vivo in a murine arthritis model and in vitro in human synovial cells. Collagen-induced arthritis was induced in mice, and after onset of arthritis the mice were treated
with DHMEQ (5 mg/kg body weight per day). Using fibroblast-like synoviocyte (FLS) cell lines established from patients with
rheumatoid arthritis (RA), NF-κB activity was examined by electrophoretic mobility shift assays. The expression of molecules
involved in RA pathogenesis was determined by RT-PCR, ELISA, and flow cytometry. The proliferative activity of the cells was
estimated with tritiated thymidine incorporation. After 14 days of treatment with DHMEQ, mice with collagen-induced arthritis
exhibited decreased severity of arthritis, based on the degree of paw swelling, the number of swollen joints, and radiographic
and histopathologic scores, compared with the control mice treated with vehicle alone. In RA FLS stimulated with tumor necrosis
factor-α, activities of NF-κB components p65 and p50 were inhibited by DHMEQ, leading to suppressed expression of the key
inflammatory cytokine IL-6, CC chemokine ligand-2 and -5, matrix metalloproteinase-3, intercellular adhesion molecule-1, and
vascular cell adhesion molecule-1. The proliferative activity of the cells was also suppressed. This is the first demonstration
of an inhibitor of NF-κB nuclear translocation exhibiting a therapeutic effect on established murine arthritis, and suppression
of inflammatory mediators in FLS was thought to be among the mechanisms underlying such an effect. 相似文献
12.
JM Kim EM Noh KB Kwon JS Kim YO You JK Hwang BM Hwang BS Kim SH Lee SJ Lee SH Jung HJ Youn YR Lee 《Phytomedicine》2012,19(12):1085-1092
Curcumin (diferuloylmethane) is a polyphenol derived from the plant turmeric (Curcuma longa), which is commonly used as a spice. Although anti-carcinogenic, anti-oxidant, anti-inflammation, and anti-angiogenic properties have been reported, the effect of curcumin on breast cancer metastasis is unknown. Matrix metalloproteinase-9 (MMP-9) is a major component in cancer cell invasion. In this study, we investigated the inhibitory effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion and the molecular mechanisms involved in MCF-7 cells. Our results showed that curcumin inhibits TPA-induced MMP-9 expression and cell invasion through suppressing NF-κB and AP-1 activation. Also, curcumin strongly repressed the TPA-induced phosphorylation of p38 and JNK and inhibited TPA-induced translocation of PKCα from the cytosol to the membrane, but did not affect the translocation of PKCδ. These results indicate that curcumin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKCα, MAPK and NF-κB/AP-1 pathway in MCF-7 cells. Curcumin may have potential value in restricting breast cancer metastasis. 相似文献
13.
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
14.
Sammy Grimaldo Fang Tian Lu-Yuan Li 《Apoptosis : an international journal on programmed cell death》2009,14(6):788-795
Vascular endothelial growth inhibitor (VEGI) is an endogenous inhibitor of endothelial cell growth and a promising candidate
for cancer therapy. VEGI is able to inhibit tumor growth by specifically targeting the tumor neovasculature. Increasing the
anti-angiogenic potential of this cytokine is of great interest for its therapeutic potential. NF-κB is known to have an integral
role in TNF superfamily signaling, acting as a pro-survival factor. A role of VEGI-induced NF-κB activation in endothelial
cells has yet to be described. Here we show that suppression of the NF-κB pathway can increase the apoptotic potential of
VEGI. We used siRNA to deplete NF-κB or its activator IKK2 from adult bovine aortic endothelial cells. The siRNA treatments
diminished VEGI-induced NF-κB activation, evidenced from a reduced extent of NF-κB nuclear translocation and diminished expression
of NF-κB-target genes such as interleukins-6 and -1β. The siRNA-treated endothelial cells when exposed to VEGI exhibited a marked decrease in cell viability and a significant
increase in apoptosis. These results confirm that VEGI utilizes NF-κB as a pro-survival role factor in endothelial cells.
We then examined whether a combination of VEGI with NF-κB inhibitors would constitute a more potential therapeutic regiment.
We found that in the presence of the NF-κB inhibitors curcumin or BMS-345541 there was a marked increase in the apoptotic
potential of VEGI on endothelial cells. These findings indicate that a combination therapy using VEGI and NF-κB inhibitors
could be a potent approach for cancer treatment. 相似文献
15.
Lixia Chen Guoqing Tian Changxia Shao Everardo Cobos Weimin Gao 《Molecular biology reports》2010,37(7):3105-3110
Curcumin, a polyphenolic compound, is the active component of Curcuma longa and has been extensively investigated as an anticancer drug that modulates multiple pathways. Eukaryotic initiation factors
(eIFs) have been known to play important roles in translation initiation, which controls cell growth and proliferation. Little
is known about the effects of curcumin on eIFs in lung cancer. The objective of this study was to exam the curcumin cytotoxic
effect and modulation of two major rate-limiting translation initiation factors, including eIF2α and eIF4E protein expression
levels in lung adenocarcinoma epithelial cell line A549. Cytotoxicity was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide) assay and protein changes were determined by Western blot. A549 cells were treated with 0–240 μM curcumin for 4–96 h.
The inhibitory effects of curcumin on cytotoxicity were dose- and time-dependent (P < 0.001). The 50% inhibitory curcumin concentrations (IC50s) at 24, 48, 72, and 96 h were 93, 65, 40, and 24 μM, respectively.
Protein expressions of eIF2α, eIF4E, Phospho-4E-BP1 were down-regulated, while Phospho-eIF2α and Phospho-eIF4E were up-regulated
after A549 cells were treated with 20 and 40 μM curcumin for 24 h. In addition, the effects of curcumin on these protein expression
changes followed a significant dose-response (P < 0.05, trend test). These findings suggest that curcumin could reduce cell viability through prohibiting the initiation
of protein synthesis by modulating eIF2α and eIF4E. 相似文献
16.
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
17.
18.
19.
Osteopontin (OPN) is a secreted, non-collagenous, sialic-acid rich, glycosylated adhesive phospho- protein. Several highly
metastatic transformed cells synthesized a higher level of OPN compared with non-tumorigenic cells. We have recently reported
that OPN induces nuclear factor-κB (NF-κB)-mediated promatrix metalloproteinase-2 activation through IκBα/IKK signaling pathways.
However, the molecular mechanism(s) by which OPN regulates pro-matrix metalloproteinase-9 (pro-MMP-9) activation and involvement
of upstream kinases in regulation of these processes that ultimately control cell motility and tumor growth in murine melanoma
cells are not well defined. Here we report that OPN induces αvβ3 integrin-mediated phosphorylation and activation of nuclear
factor inducing kinase (NIK) and enhances the interaction between phosphorylated NIK and IκBα kinase α/β (IKKα/β) in B16F10
cells. Moreover, NIK is involved in OPN-induced phosphorylations of MEK-1 and ERK1/2 in these cells. OPN induces NIK-dependent
NF-κB activation through ERK/IKKα/β-mediated pathways. Furthermore, OPN enhances NIK-regulated urokinase-type plasminogen
activator (uPA) secretion, uPA-dependent pro-MMP-9 activation, and cell motility. Pretreatment of cells with anti-MMP-2 antibody
along with anti-MMP-9 antibody drastically inhibited the OPN-induced cell migration and chemoinvasion, whereas cells pretreated
with anti-MMP-2 antibody had no effect on OPN-induced pro-MMP-9 activation suggesting that OPN induces pro-MMP-2 and pro-MMP-9
activations through two distinct pathways. Taken together, NIK acts as crucial regulator in OPN-induced MAPK/IKK-mediated
NF-κB-dependent uPA secretion and MMP-9 activation thereby controlling melanoma cell motility and chemoinvasion.
An erratum to this article is available at . 相似文献
20.
Yuan-Wei Shih Shang-Tao Chien Pin-Shern Chen Jian-Hui Lee Shu-Hau Wu Li-Te Yin 《Cell biochemistry and biophysics》2010,58(1):31-44
The purpose of this study is to investigate the anti-metastatic effect of α-mangostin on phorbol 12-myristate 13-acetate (PMA)-induced
matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions in A549 human lung adenocarcinoma cells.
Firstly, α-mangostin could inhibit PMA-induced abilities of the adhesion, invasion, and migration. Data also showed α-mangostin
could inhibit the activation of αvβ3 integrin, focal adhesion kinase (FAK), and extracellular signal-regulated kinase1/2 (ERK1/2)
involved in the downregulation the enzyme activities, protein and messenger RNA levels of MMP-2 and MMP-9 induced by PMA.
Next, α-mangostin also strongly inhibited PMA-induced degradation of inhibitor of kappaBα (IκBα) and the nuclear levels of
nuclear factor kappa B (NF-κB). Also, a dose-dependent inhibition on the binding abilities of NF-κB by α-mangostin treatment
was further observed. Furthermore, reduction of FAK or ERK1/2 phosphorylation by FAK small interfering RNA (FAK siRNA) potentiated
the effect of α-mangostin. Finally, the transient transfection of ERK siRNA significantly down-regulated the expressions of
MMP-2 and MMP-9 concomitantly with a marked inhibition on cell invasion and migration. Presented results indicated α-mangostin
is a novel, effect, anti-metastatic agent that functions by downregulating MMP-2 and MMP-9 gene expressions. 相似文献