共查询到20条相似文献,搜索用时 31 毫秒
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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
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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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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
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Rainer Voisard Nicola Huber Regine Baur Milorat Susa Oliver Ickrath Anton Both Wolfgang Koenig Vinzenz Hombach 《BMC molecular biology》2001,2(1):7-7
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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12.
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Tumor necrosis factor alpha (TNFα) activates the nuclear factor-kappaB (NF-κB) pathway in various cell types, leading to expression
of cell survival and inflammatory proteins. One mechanism of cell survival brought about by NF-κB is the inhibition of Activator
Protein-1 (AP-1), which when activated, could lead to cell death. However, TNFα can also induce the AP-1 pathway, and the
mechanisms by which these two pathways are regulated in response to TNFα are poorly understood. We proposed that Inhibitor
of κB Kinase gamma (IKKγ) (which is also known as NF-κB essential modulator, NEMO) plays a key role in integrating and coordinating
these two pathways. Our results showed that IKKγ activates the AP-1 pathway, via a mechanism that is dependent on the first
leucine zipper (LZ) domain of IKKγ, by interacting with two proteins of the AP-1 complex, c-Jun and c-Fos, and changing the
phosphorylation status of c-Jun. Even though IKKγ is required for the activation of NF-κB, we found that it reduced the activity
of NF-κB when it was overexpressed. In summary, we demonstrated that transfected IKKγ, while inhibiting the NF-κB pathway,
directly interacts with the AP-1 proteins and activates the AP-1 pathway independent of its effects on NF-κB. Our results
indicate that IKKγ regulates TNFα signaling by coordinating cell responses mediated by the AP-1 and NF-κB pathways.
A. S. Shifera and J. M. Friedman contributed equally to this article.
Marshall S. Horwitz—Deceased: This article is dedicated to his loving memory. 相似文献
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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
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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