共查询到20条相似文献,搜索用时 15 毫秒
1.
Calvaruso G Giuliano M Portanova P De Blasio A Vento R Tesoriere G 《Molecular and cellular biochemistry》2006,287(1-2):13-19
Abstact The present paper demonstrates that the proteasome inhibitor bortezomib, which behaves as an apoptotic agent in hepatoma HepG2 cells, caused in these cells a decrease in IκBα level and a consequent increase in NF-κB activity. The effect already appeared at 4 h of treatment and preceded the onset of apoptosis which was observed at 24 h. Our results demonstrate that bortezomib-induced IκBα degradation occurred in conjunction with the activation of caspase-8; moreover, the decrease in IκBα level was prevented in a dose-dependent manner by the addition of z-IETD, a specific inhibitor of caspase-8. Bortezomib caused the same effects in non-tumor Chang liver cells, which were not susceptible to the apoptotic effect of the drug. Our results also show that other proteases, such as caspase-3 and calpains, exerted only a limited effect on IκBα degradation. These findings suggest that caspase-8 can be involved in the control of IκBα level. In addition, the activation of caspase-8 can exert, at least in the first phase of treatment with bortezomib, a protective effect in both HepG2 and Chang liver cells, favouring the activation of the survival factor NF-κB 相似文献
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3.
Kapral M Węglarz L Parfiniewicz B Lodowska J Jaworska-Kik M 《Folia microbiologica》2010,55(6):657-661
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
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6.
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
7.
Lee S Park HH Son HY Ha JH Lee MG Oh TY Sohn DH Jeong TC Lee SH Son JK Lee SG Jun CD Kim SH 《Cell biology and toxicology》2007,23(2):105-112
Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis.
Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin
(IL)-1β and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated
the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied
its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-α, IL-1β,
and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601
attenuated PMA- and A23187-induced activation of NF-κB as indicated by inhibition of degradation of IκBα, nuclear translocation
of NF-κB, NF-κB/DNA binding, and NF-κB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases. 相似文献
8.
Johannes Witt Sandra Barisic Eva Schumann Frank Allg?wer Oliver Sawodny Thomas Sauter Dagmar Kulms 《BMC systems biology》2009,3(1):71
Background
Biological effects of nuclear factor-κB (NFκB) can differ tremendously depending on the cellular context. For example, NFκB induced by interleukin-1 (IL-1) is converted from an inhibitor of death receptor induced apoptosis into a promoter of ultraviolet-B radiation (UVB)-induced apoptosis. This conversion requires prolonged NFκB activation and is facilitated by IL-1 + UVB-induced abrogation of the negative feedback loop for NFκB, involving a lack of inhibitor of κB (IκBα) protein reappearance. Permanent activation of the upstream kinase IKKβ results from UVB-induced inhibition of the catalytic subunit of Ser-Thr phosphatase PP2A (PP2Ac), leading to immediate phosphorylation and degradation of newly synthesized IκBα. 相似文献9.
Mao-hong Zhou Jian-she Ma Jun Li Hai-ren Ye Ke-xin Huang Xiao-wei Zhao 《Biotechnology and Bioprocess Engineering》2008,13(5):545-551
A bacterial strain able to produce κ-carrageenase, designated WZUC10, was isolated from a live specimen of the red alga Plocamium telfainae collected in the East China Sea. The phylogenetic evidence and phenotypic features indicate that this strain belongs to the
genus Pseudoalteromonas. WZUC10 requires NaCl for growth and κ-carrageenan to induce κ-carrageenase synthesis; galactose and lactose do not induce
it. The optimal growth temperature is 23∼27°C. The secreted enzyme, which has a molecular mass of 45 kDa, breaks down κ-carrageenan
into κ-neocarratetraose sulfate and larger oligosaccharides with a repeating β-D-Galp4S-(1→4)-α-D-AnGalp structure, but cannot degrade κ-neocarratetraose sulfate or κ-neocarrahexaose sulfate into κ-neocarrabiose sulfate. The enzyme
retains 90% of its activity after 2 h at 40°C and is completely inactivated after 7.5 min at 70°C. The enzyme’s optimal temperature
is 30°C and its optimal pH is 7.5. The enzyme-catalyzed reaction follows Michaelis-Menten kinetics, with the Michaelis constant
(K
m) and the turnover number (k) being 0.015 mM and 125 s−1, respectively. WZUC10 produces 50 U/mL κ-carrageenase after cultivation at 25°C for 35 h on a medium containing 80 g/L glucose,
5 g/L corn steep liquor, 3 g/L κ-carrageenan, and 15 g/L NaCl. κ-Neocarratetraose sulfate was prepared simply with precipitation
by ethanol:water (5:1, v/v). 相似文献
10.
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
11.
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
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.
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
14.
Chemokine and chemokine receptor expression in gingival tissues plays a central role in periodontal disease during aging.
In the present study, we explored the modulation of chemokines and chemokine receptors expression in aging rat gingival tissues.
In the 24-month-old (Old) rat gingival tissues, RANTES and CCR5 mRNA and protein levels were 2–4 fold increased over those
of the 6-month-old (Young) rats. The Old rats had considerable enhancement of all three of the studied MAPK activities: extracellular
signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. These results suggest that age-related increases in RANTES and CCR5 expression are associated
with increased IκBα, nuclear NF-κB, and MAPK activity in gingival tissues. 相似文献
15.
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
16.
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
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The mechanism by which lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) induces production of proinflammatory
cytokines in murine macrophages, and the role of phosphatidylinositol 3-kinase (PI3-kinase) have not been well investigated.
Activation of nuclear factor κB (NF-κB) is initiated by the phosphorylation of the inhibitory subunit, IκB, which targets
IκB for degradation and leads to the release of active NF-κB. In this study we demonstrate that 2- (4-morpholinyl)-8-phenylchromone
(LY294002), which inhibits PI3-kinase, specifically inhibited degradation of IκBα in RAW264.7 cells stimulated with interferon-γ
(IFN-γ) plus LPS or IFN-γ plus PMA. To elucidate the importance of this activity in RAW264.7 cells, we examined tumor necrosis
factor-α (TNF-α) and interleukin IL)-6 production in the activated cells. Pretreatment of the cells with LY294002 resulted
in the inhibition of TNF-α and IL-6 production in RAW264.7 cells stimulated with IFN-γ plus LPS or IFN-γ plus PMA. Furthermore,
LY294002 inhibited the production of nitric oxide NO) in RAW264.7 cells stimulated with IFN-γ plus LPS or IFN-γ plus PMA.
LY294002 also inhibited inducible NO synthase (iNOS) mRNA expression in the activated RAW264.7 cells. In conclusion, the present
results suggest that PI3-kinase is involved in the signal transduction pathway responsible for LPS- or PMA-mediated TNF-α
and IL-6 production, and that LY294002 inhibits NO generation through blocking the degradation of IκBα in activated RAW264.7
cells.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
20.
The phylogeny and geography of the medaka (Oryzias latipes) populations of Korea were investigated by analyzing sequence data for the mitochondrial control region. From the 41 haplotypes including 25 Korean haplotypes detected in 64 Korean specimens and data for the Japanese and Chinese populations, phylogenetic and nested clade analyses were executed to examine the phylogeny of haplogroups and the relation of the genetic architecture of the haplotypes to the historical geography of the Korean medaka fish. The analyses suggest that there are two very distinct lineages of Korean medaka, and that these result from reproductive isolation mechanisms due to geographic barriers. The southeastern lineage has experienced recent range expansion to the western region. The northwestern lineage, sister to Chinese populations, showed evidence of internal range expansion with shared haplotypes. 相似文献