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1.
A d-galactose-specific lectin, MW = 40 kDa, had been purified from pupae of Musca domestica (MPL). MPL significantly promoted the proliferation of B cells and enhanced the production of IL-12 in a dose-dependent manner.
MPL stimulated IκB-α degradation, NF-κB translocation and ERK1/2 phosphorylation which played an upstream role for NF-кB in
MPL-induced B cells. Moreover, MPL regulated cell proliferation and induced IL-12 production through ERK1/2-NF-κB signaling
pathway. 相似文献
2.
3.
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
4.
Dedifferentiated hepatoma cells, in contrast to most other cell types including hepatoma cells, undergo apoptosis when treated
with lipopolysaccharide (LPS) plus the protein synthesis inhibitor cycloheximide (CHx). We recently reported that the dedifferentiated
hepatoma cells also exhibit a strong and prolonged NF-κB induction phenotype upon exposure to LPS, suggesting that NF-κB signaling
may play a pro-survival role, as reported in several other cell systems. To test the role of NF-κB in preventing LPS-mediated
apoptosis, we examined the dedifferentiated cell line M38. Results show that antioxidants strongly inhibited LPS + CHx-mediated
cell death in the M38 cells, yet only modestly inhibited NF-κB induction. In addition, inhibition of NF-κB translocation by
infection of the M38 cells with an adenoviral vector expressing an IκBα super-repressor did not result in LPS-mediated cell
death. These results suggest that unlike TNFα induction, the cell survival pathway activated in response to LPS is independent
of NF-κB translocation in the dedifferentiated cells. Addition of inhibitors of JNK, p38 and ERK pathways also failed to elicit
LPS-mediated apoptosis similar to that observed when protein synthesis is prevented. Thus, cell survival pathways other than
those involving NF-κB inducible gene expression or other well-known pathways appear to be involved in protecting the dedifferentiated
hepatoma variant cells from LPS-mediated apoptosis. Importantly, this pro-apoptotic function of LPS appears to be a function
of loss of hepatic gene expression, as the parental hepatoma cells resist LPS-mediated apoptosis in the presence of protein
synthesis inhibitors. 相似文献
5.
Ceramide causes either apoptosis or non-apoptotic cell death depending on model system and experimental conditions. The present
study was undertaken to examine the effect of ceramide on cell viability and its molecular events leading to cell death in
A172 human glioma cells. Ceramide induced cell death in a dose-dependent manner and the cell death was dependent on generation
of reactive oxygen species and lipid peroxidation. TUNEL assay, Hoechst 33258 staining, and flow cytometric analysis did not
show typical apoptotic morphological features. Ceramide caused phosphorylation of extracellular signal-regulated kinase (ERK)
and p38, but the cell death was not affected by inhibitors of MAPK subfamilies. Ceramide caused ATP depletion without loss
of mitochondrial membrane potential. Ceramide did not induce caspase activation and ceramide-induced cell death was also not
altered by inhibitors of caspase activation. Transfection of dominant inhibitory mutant of IκBα (S32A/36A) and pretreatment
of pyrrolidinedithiocarbamate, an inhibitor of NF-κB, enhanced ceramide-induced cell death. These results indicate that ceramide
causes non-apoptotic, caspase-independent cell death by inducing reactive oxygen species generation in A172 human glioma cells.
NF-κB is involved in the regulation of ceramide-induced cell death in human glioma cells. 相似文献
6.
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
7.
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
8.
Hongmei Liu Congcong Zhang Kaixun Huang 《Journal of biological inorganic chemistry》2011,16(5):671-681
Experimental studies have demonstrated that oral administration of lanthanum chloride (LaCl3) inhibits the development of atherosclerosis, but the related mechanism has not been fully elucidated. Oxysterols are toxic
to the vascular endothelial cells which are important in preventing the formation and progression of atheromatous plaque.
In this study, we examined the effect of LaCl3 on oxysterol cholestane-3β,5α,6β-triol (Triol)-induced apoptosis and the related mechanisms in ECV-304 cells, a presumptive
endothelial cell line. Incubation with Triol resulted in apoptosis of ECV-304 cells, as determined by Hoechst 33342 staining,
fluorescein isothiocyanate labeled annexin V/propidium iodide double staining, and the loss of mitochondrial membrane potential.
Triol activated extracellular-signal-regulated kinase (ERK) and nuclear factor κB (NF-κB), and inhibition of Triol-activated
ERK and NF-κB signaling by specific inhibitors attenuated apoptosis induction by Triol in ECV-304 cells. Pretreatment with
LaCl3 (1 μM) for 12 h before exposure to Triol decreased Triol-mediated apoptosis as well as activation of ERK and NF-κB. In addition,
Triol induced oxidative stress in ECV-304 cells, manifested by the increase of intracellular reactive oxygen species generation
and malondialdehyde level, and the reduction of the content of total protein thiols and the activity of antioxidant glutathione
peroxidases; LaCl3 pretreatment significantly reversed these effects. Finally, LaCl3 pretreatment significantly inhibited the increases of intracellular Ca2+ concentration induced by Triol. Our study suggests that Triol induced ECV-304 cell apoptosis, and LaCl3 could suppress this effect probably by inhibiting intracellular Ca2+ concentration elevation, oxidative stress, as well as activation of ERK and NF-κB signaling pathways. 相似文献
9.
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
10.
Hochhauser E Pappo O Ribakovsky E Ravid A Kurtzwald E Cheporko Y Lelchuk S Ben-Ari Z 《Apoptosis : an international journal on programmed cell death》2008,13(1):77-86
Introduction Apoptosis is a central mechanism of cell death following reperfusion of the ischemic liver. Recombinant human erythropoietin
(rhEPO) have an important role in the treatment of myocardial ischemia/reperfusion (I/R) injury, by preventing apoptosis.
The aim of the study was to investigate the effect of different regimens of rhEPO in preventing apoptosis following I/R-induced
hepatic injury.
Material and methods Isolated mouse livers were randomly divided into five groups: (1) control group, perfused for the whole study period (105 min);
(2) 30-min perfusion followed by 90 min of ischemia and 15 min of reperfusion; (3), (4) and (5) like group 2, but with administration
of rhEPO 5,000 units/kg i.p. at 30 min, 24 h, or both 30 min and 24 h respectively, before induction of ischemia. Perfusate
liver enzyme levels and intrahepatic caspase-3 activity were measured, and apoptotic cells were identified by morphological
criteria, TUNEL assay, and immunohistochemistry for caspase-3. Using immunoblot the expression of the proapoptotic JNK and
inhibitor of NFκB (IκBα) were also evaluated. von Willebrand factor (vWF) immunohistochemistry was used as a marker of endothelial
cells.
Results Compared to the I/R livers, all 3 rhEPO pretreated groups showed: a significant reduction in liver enzyme levels (P < 0.05) and intrahepatic caspase-3 activity (P < 0.05), fewer apoptotic hepatocytes (P < 0.05) and positive vWF staining in numerous endothelial cells lining the sinusoids. EPO decreased JNK phosphorylation and
the degradation of the inhibitor of NFκB (IκBα) during I/R. There was no added benefit of the multiple- over the single-dose
rhEPO regimen.
Conclusion Pretreatment with one dose of rhEPO can attenuate post-I/R hepatocyte apoptotic liver damage. NFκB and JNK activation is likely
to play a pivotal role in the pathophysiology of I/R hepatic injury and might have a key role in EPO-mediated protective effects.
This effect is associated with the increase in sinusoidal vWF immunostaining suggests an additional effect of rhEPO in liver
angiogenesis recovery. These findings have important implications for the potential use of rhEPO in I/R injury during liver
transplantation.
Edith Hochhauser and Orit Pappo are first two coauthors. 相似文献
11.
Qunying Hong Li-Jin Hsu Lori Schultz Nicole Pratt Jeffrey Mattison Nan-Shan Chang 《BMC molecular biology》2007,8(1):50
Background
Zfra is a 31-amino-acid zinc finger-like protein, which is known to regulate cell death by tumor necrosis factor (TNF) and overexpressed TNF receptor- or Fas-associated death domain proteins (TRADD and FADD). In addition, Zfra undergoes self-association and interacts with c-Jun N-terminal kinase 1 (JNK1) in response to stress stimuli. To further delineate the functional properties of Zfra, here we investigated Zfra regulation of the activation of p53, WOX1 (WWOX or FOR), NF-κB, and JNK1 under apoptotic stress. 相似文献12.
The present study attempts to investigate the effects of S-propargyl-cysteine (SPRC), a sulfur-containing amino acid, on lipopolysaccharide (LPS)-induced inflammatory response in H9c2
cardiac myocytes. We found that SPRC prevented nuclear factor-κB (NF-κB) activation assessed by NF-κB p65 phosphorylation
and IκBα degradation, suppressed LPS-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and intracellular
reactive oxygen species (ROS) production. Furthermore, incubation of H9c2 cells with SPRC induced phosphorylation of Akt in
a time- and concentration-dependent manner. In addition, SPRC attenuated LPS-induced mRNA and protein expression of tumor
necrosis factor-α (TNF-α), and mRNA expression of intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase
(iNOS). The effects of SPRC were abolished by cystathionine γ-lyase [CSE-an enzyme that synthesizes hydrogen sulfide (H2S)] inhibitor, dl-propargylglycine (PAG), SPRC-induced Akt phosphorylation and TNF-α release was also abolished by the phosphoinositide 3-kinase
(PI3K) inhibitor LY294002. Furthermore, SPRC also increased LPS-induced down-regulation expression of CSE and H2S level in H9c2 cells. PAG abolished SPRC-induced up-regulation of H2S level. Therefore, we concluded that SPRC produced an anti-inflammatory effect in LPS-stimulated H9c2 cells partly through
the CSE/H2S pathway by impairing IκBα/NF-κB signaling and by activating PI3K/Akt signaling pathway. 相似文献
13.
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14.
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
15.
16.
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
17.
Amrie C Grammer Randy Fischer Olivia Lee Xuan Zhang Peter E Lipsky 《Arthritis research & therapy》2003,6(1):28
Abnormalities in lymphocyte signaling cascades are thought to play an important role in the development of autoimmune disease.
However, the large amount of cellular material needed for standard biochemical assessment of signaling status has made it
difficult to evaluate putative abnormalities completely using primary lymphocytes. The development of technology to employ
intracellular staining and flow cytometry to assess the signaling status of individual cells has now made it possible to delineate
the perturbations that are present in lymphocytes from patients with autoimmune disease. As an example, human B cells from
the Ramos B cell line and the periphery of systemic lupus erythematosus (SLE) patients or normal nonautoimmune controls were
assessed for activation of the NF-κB and mitogen activated protein kinase (MAPK) signaling cascades by intracellular multiparameter
flow cytometric analysis and biochemical Western blotting. In combination with fluorochrome conjugated antibodies specific
for surface proteins that define B cell subsets, antibodies that recognize activated, or phosphorylated inhibitors of κB (IκB)
as well as the extracellular regulated kinase (ERK), jun N-terminal kinase (JNK) or p38 MAPKs were used to stain fixed and
permeabilized human B cells and analyze them flow cytometrically. Examination of the known signaling pathways following engagement
of CD40 on human B cells confirmed that intracellular flow cytometry and Western blotting equivalently assay CD154-induced
phosphorylation and degradation of IκB proteins as well as phosphorylation of the MAPKs ERK, JNK and p38. In addition, B cells
from the periphery of SLE patients had a more activated status immediately ex vivo as assessed by intracellular flow cytometric analysis of phosphorylated ERK, JNK and p38 when compared with B cells from
the periphery of normal, nonautoimmune individuals. Together, these results indicate that multiparameter intracellular flow
cytometric analysis of signaling pathways, such as the NF-κB and MAPK cascades, can be used routinely to assess the activation
status of a small number of cells and thus delineate abnormalities in signaling molecules expressed in primary lymphocytes
from patients with autoimmune disease. 相似文献
18.
Cacalano NA Le D Paranjpe A Wang MY Fernandez A Evazyan T Park NH Jewett A 《Apoptosis : an international journal on programmed cell death》2008,13(12):1439-1449
The aim of this study is to identify potential gene and protein targets when nuclear factor kappa B (NFκB) and c-jun N-terminal
kinase (JNK) were inversely expressed in oral tumors. To determine which genes were regulated synergistically by the inverse
expression of NFκB and JNK, a pathway specific microarray analysis was performed. While either inhibition of NFκB or activation
of JNK alone was unable to affect the IGFBP6 gene expression in microarray analysis, concomitant increase in JNK activation
in the presence of NFκB inhibition increased the expression of this gene significantly. Synergistic increase in IGFBP6 gene
expression was also confirmed by RT-PCR and Northern blot analysis of transfected cells. Accordingly, the levels of IGFBP6
protein secretion rose synergistically when JNK was over-expressed in NFκB knock down cells. In addition, increased expression
of JNK in the absence of NFκB resulted in a significant induction of cell death in oral tumors when either left untreated
or treated with TNF-α and TPA. Moreover, when JNK was inhibited by dominant negative JNK (APF), a significant decrease in
cell death could be observed in TNF-α and TPA treated NFκB knock down oral tumors. Therefore, increased induction of IGFBP6
gene or protein expression in oral tumors could be regarded as a potential predictive marker of tumor sensitivity and could
be used for prognostic purposes, since a significant correlation could be observed between increased induction of apoptotic
cell death and elevated levels of IGFBP6 in these tumors. 相似文献
19.
H2 is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis,
may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. LOX-1 expression can be upregulated by various
stimuli, including TNF-α. Thus, we aimed to examine whether the upregulation of LOX-1 by different stimuli could be blocked
by H2 in endothelial cells. H2 significantly abolished the upregulation of LOX-1 by different stimuli, including TNF-α, at the protein and mRNA levels.
The TNF-α-induced upregulation of LOX-1 was also attenuated by the NF-κB inhibitor N-acetyl-l-cysteine. H2 inhibited the TNF-α-induced activation of NF-κB and the phosphorylation of IκB-α. Furthermore, H2 inhibited the expression of LOX-1 and the activation of NF-κB in apolipoprotein E knockout mice, an animal model of atherosclerosis.
Thus, H2 probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-κB activation. 相似文献