共查询到20条相似文献,搜索用时 15 毫秒
1.
Chatterjee A Mir SA Dutta D Mitra A Pathak K Sarkar S 《Journal of cellular physiology》2011,226(10):2543-2554
Cardiac hypertrophy leading to eventual heart failure is the most common cause of mortality throughout the world. The triggering mechanisms for cardiac hypertrophy are not clear but both apoptosis and cell proliferation have been reported in sections of failing hearts. In this study, we utilized both angiotensin II (AngII) treatment of cardiomyocytes and aortic ligation in rats (Rattus norvegicus, Wistar strain) for induction of hypertrophy to understand the cellular factors responsible for activation of apoptotic or anti-apoptotic pathway. Hypertrophy markers (ANF, β-MHC), apoptotic proteins (Bax, Bad, Fas, p53, caspase-3, PARP), and anti-apoptotic or cell proliferation marker proteins (Bcl2, NF-κB, Ki-67) were induced significantly during hypertrophy, both in vitro as well as in vivo. Co-localization of both active caspase-3 and Ki-67 was observed in hypertrophied myocytes. p53 and NF-κBp65 binding to co-activator p300 was also increased in AngII treated myocytes. Inhibition of p53 resulted in downregulation of apoptosis, NF-κB activation, and NF-κB-p300 binding; however, NF-κB inhibition did not inhibit apoptosis or p53-p300 binding. Blocking of either p53 or NF-κB by specific inhibitors resulted in decrease in cell proliferation and hypertrophy markers, suggesting that p53 initially binds to p300 and then this complex recruits NF-κB. Thus, these results indicate the crucial role of p53 in regulating both apoptotic and cell proliferation during hypertrophy. 相似文献
2.
Rajapurohitam V Kilic A Javadov S Karmazyn M 《Molecular and cellular biochemistry》2012,366(1-2):287-297
We recently identified leptin as a downstream factor mediating the hypertrophic effects of both angiotensin II and endothelin-1 in cardiomyocytes, an effect dependent on increased leptin biosynthesis, however, the mechanism for such increased leptin production is not known. This study was designed to elucidate the mechanisms underlying angiotensin II- and endothelin-1-stimulated synthesis in cultured ventricular myocytes. The hypertrophic effects of both angiotensin II (100 nM) and endothelin-1 (10 nM) were associated with increased leptin secretion and gene expression by 40 and 50 %, and 86 and 68 %, respectively. These effects were associated with significantly increased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation by 34 and 52 %, as well as enhanced translocation of NF-κB into nuclei and also the NF-κB-DNA binding activity by 35 and 31 % induced by angiotensin II and endothelin-1, respectively. On their own, 24 h treatment with either angiotensin II or endothelin-1 increased cell surface area by 30 and 40 %, protein synthesis by 30 % and the α-skeletal actin gene by 53 and 68 %, respectively, indicating a robust hypertrophic effect whereas this was completely prevented by NF-κB inhibition. In addition, NF-κB inhibition significantly attenuated angiotensin II and endothelin-1-induced p38 MAPK activation whereas inhibition of p38 MAPK blocked both angiotensin II- and endothelin-1-induced increases in leptin secretion. The ability of both angiotensin II- and endothelin-1 to increase leptin production in cardiomyocytes and the resultant hypertrophic response are mediated by NF-κB and dependent on p38 MAPK activation. 相似文献
3.
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
4.
Hyo Sang Jo Eun Ji Yeo Min Jea Shin Yeon Joo Choi Hyeon Ji Yeo Su Bin Cho Jung Hwan Park Chi Hern Lee Won Sik Eum Soo Young Choi 《Biotechnology letters》2017,39(4):511-521
Objectives
To identify the protective effect of DJ-1 protein against oxidative stress-induced HepG2 cell death, we used cell-permeable wild type (WT) and a mutant (C106A Tat-DJ-1) protein.Results
By using western blotting and fluorescence microscopy, we observed WT and C106A Tat-DJ-1 proteins were efficiently transduced into HepG2 cells. Transduced WT Tat-DJ-1 proteins increased cell survival and protected against DNA fragmentation and intracellular ROS generation levels in H2O2-exposed HepG2 cells. At the same time, transduced WT Tat-DJ-1 protein significantly inhibited NF-κB and MAPK (JNK and p38) activation as well as regulated the Bcl-2 and Bax expression levels. However, C106A Tat-DJ-1 protein did not show any protective effect against cell death responses in H2O2-exposed HepG2 cells.Conclusions
Oxidative stress-induced HepG2 cell death was significantly reduced by transduced WT Tat-DJ-1 protein, not by C106A Tat-DJ-1 protein. Thus, transduction of WT Tat-DJ-1 protein could be a novel strategy for promoting cell survival in situations of oxidative stress-induced HepG2 cell death.5.
6.
Retinoids have been shown to inhibit the growth and modulate the glycosylation of head and neck squamous cell carcinoma (HNSCC) cells including the MDA886Ln cells. To examine the effects of -all-trans retinoic acid (RA) on glycoconjugates in HNSCC MDA886Ln cells, the cells were grown in the absence or presence of 1 µM RA and then labeled with tritiated monosaccharides, extracted and analysed by polyacrylamide gel electrophoresis and fluorography. RA increased markedly the incorporation of [3H]-glucosamine, [3H]-galactose, and [3H]-mannose into numerous cellular glycoconjugates, however, the incorporation of [3H]-fucose and [3H]-leucine was almost unaffected by RA. RA increased the incorporation of glucosamine and galactose but not mannose into high molecular weight (HMW) glycoconjugates of about 220 and 500–600 kDa. To analyse the steady state level of glycoconjugates by lectin blotting, extracts of unlabeled cells were separated by gel electrophoresis and the gels were probed with125I-labeled wheat germ agglutinin (WGA) andMaackia amurensis (MA) agglutinin. Both lectins were found to bind to numerous glycoconjugates including the HMW glycoconjugates, whereas125I-peanut agglutinin bound only to the HMW glycoconjugates. RA treatment increased the binding of all three lectins to the HMW glycoconjugates. These findings demonstrate that RA enhanced the incorporation of specific monosaccharides into a variety of glycoconjugates and in particular into HMW mucin-like glycoconjugates. This effect of RA may be the result of induction of a more normal differentiation state of the HNSCC cells. 相似文献
7.
Jung Ok Ban Dong Hoon Kwak Ju Hoon Oh Eun-Jung Park Min-Chul Cho Ho Seub Song Min Jong Song Sang Bae Han Dong Cheul Moon Keon Wook Kang Jin Tae Hong 《Chemico-biological interactions》2010,188(1):75-85
Peroxisome proliferator-activated receptor (PPAR)-γ agonists such as troglitazone, pioglitazone and thiazolidine have been shown to induce apoptosis in human colon cancer cells. The molecular mechanism of PPARγ agonist-induced apoptosis of colon cancer cells, however, is not clear. Glycogen synthase kinase-3β (GSK-3β) is an indispensable element for the activation of nuclear factor-kappa B (NF-κB) which plays a critical role in the mediation of survival signals in cancer cells. To investigate the mechanisms of PPARγ agonist-induced apoptosis of colon cancer cells, we examined the effect of troglitazone (0–16 μM) on the activation of GSK-3β and NF-κB. Our study showed that the inhibitory effect of troglitazone on colon cancer cell growth was associated with inhibition of NF-κB activity and GSK-3β expression in a dose-dependent manner. Cells were arrested in G0/G1 phase followed by the induction of apoptosis after treatment of troglitazone with concomitant decrease in the expression of the G0/G1 phase regulatory proteins; Cdk2, Cdk4, cyclin B1, D1, and E as well as in the anti-apoptosis protein Bcl-2 along with an increase in the expression of the pro-apoptosis-associated proteins; Caspase-3, Caspase-9 and Bax. Transient transfection of GSK-3β recovered troglitazone-induced cell growth inhibition and NF-κB inactivation. In contrast, co-treatment of troglitazone with a GSK-3β inhibitor (AR-a014418) or siRNA against GSK-3β, significantly augmented the inhibitory effect of troglitazone on the NF-κB activity, the cancer cell growth and on the expression of G0/G1 phase regulatory proteins and pro-apoptosis regulatory proteins. These results suggest that the PPARγ agonist, troglitazone, inhibits colon cancer cell growth via inactivation of NF-κB by suppressing GSK-3β activity. 相似文献
8.
NF-κB in the Survival and Plasticity of Neurons 总被引:6,自引:0,他引:6
Mattson MP 《Neurochemical research》2005,30(6-7):883-893
9.
Go HS Seo JE Kim KC Han SM Kim P Kang YS Han SH Shin CY Ko KH 《Journal of biomedical science》2011,18(1):48
Background
At the beginning of neurogenesis, massive brain cell death occurs and more than 50% of cells are eliminated by apoptosis along with neuronal differentiation. However, few studies were conducted so far regarding the regulation of neural progenitor cells (NPCs) death during development. Because of the physiological role of cell death during development, aberration of normal apoptotic cell death is detrimental to normal organogenesis. 相似文献10.
11.
Krinninger P Brunner C Ruiz PA Schneider E Marx N Foryst-Ludwig A Kintscher U Haller D Laumen H Hauner H 《American journal of physiology. Endocrinology and metabolism》2011,300(2):E304-E311
Infiltration of immune cells into adipose tissue plays a central role in the pathophysiology of obesity-associated low-grade inflammation. The aim of this study was to analyze the role of adipocyte NF-κB signaling in the regulation of the chemokine/adipokine interferon-γ-induced protein 10 kDa (IP-10) and adipocyte-mediated T cell migration. Therefore, the regulation of IP-10 was investigated in adipose tissue of male C57BL/6J mice, primary human and 3T3-L1 preadipocytes/adipocytes. To specifically block the NF-κB pathway, 3T3-L1 cells stably overexpressing a transdominant mutant of IκBα were generated, and the chemical NF-κB inhibitor Bay117082 was used. Adipocyte-mediated T cell migration was assessed by a migration assay. It could be shown that IP-10 expression was higher in mature adipocytes compared with preadipocytes. Induced IP-10 expression and secretion were completely blocked by an NF-κB inhibitor in 3T3-L1 and primary human adipocytes. Stable overexpression of a transdominant mutant of IκBα in 3T3-L1 adipocytes led to an inhibition of basal and stimulated IP-10 expression and secretion. T cell migration was induced by 3T3-L1 adipocyte-conditioned medium, and both basal and induced T cell migration was strongly inhibited by stable overexpression of a transdominant IκBα mutant. In addition, with the use of an anti-IP-10 antibody, a significant decrease of adipocyte-induced T cell migration was shown. In conclusion, in this study, we could demonstrate that the NF-κB pathway is essential for the regulation of IP-10 in 3T3-L1 and primary human adipocytes. Adipocytes rather than preadipocytes contribute to NF-κB-dependent IP-10 expression and secretion. Furthermore, NF-κB-dependent factors and especially IP-10 represent novel signals from adipocytes to induce T cell migration. 相似文献
12.
Brian Poligone Matthew S. Hayden Luojing Chen Alice P. Pentland Eijiro Jimi Sankar Ghosh 《PloS one》2013,8(8)
Background
Previous studies have implicated NF-κB signaling in both cutaneous development and oncogenesis. However, these studies have been limited in part by the lethality that results from extreme over- or under-expression of NF-κB in available mouse models. Even cre-driven tissue specific expression of transgenes, or targeted deletion of NF-κB can cause cell death. Therefore, the present study was undertaken to evaluate a novel mouse model of enhanced NF-κB activity in the skin.Methods
A knock-in homologous recombination technique was utilized to develop a mouse model (referred to as PD mice) with increased NF-κB activity.Results
The data show that increased NF-κB activity leads to hyperproliferation and dysplasia of the mouse epidermis. Chemical carcinogenesis in the context of enhanced NF-κB activity promotes the development of keratoacanthomata.Conclusion
Our findings support an important role for NF-κB in keratinocyte dysplasia. We have found that enhanced NF-κB activity renders keratinocytes susceptible to hyperproliferation and keratoacanthoma (KA) development but is not sufficient for transformation and SCC development. We therefore propose that NF-κB activation in the absence of additional oncogenic events can promote TNF-dependent, actinic keratosis-like dysplasia and TNF-independent, KAs upon chemical carcinogensis. These studies suggest that resolution of KA cannot occur when NF-κB activation is constitutively enforced. 相似文献13.
《Biochimica et Biophysica Acta - Proteins and Proteomics》2020,1868(6):140412
Matrix metalloproteinases (MMPs) are zinc-dependent extracellular matrix remodeling endopeptidases. MMPs cleave various matrix proteins such as collagen, elastin, gelatin and casein. MMPs are often implicated in pathological processes, such as cancer progression including metastasis. Meanwhile, microorganisms produce various secondary metabolites having unique structures. We designed and synthesized dehydroxymethylepoxyquinomicin (DHMEQ) based on the structure of epoxyquinomicin C derived from Amycolatopsis as an inhibitor of NF-κB. This compound inhibited cancer cell migration and invasion. Since DHMEQ is comparatively unstable in the body, we designed and synthesized a stable DHMEQ analog, SEMBL. SEMBL also inhibited cancer cell migration and invasion. We also looked for inhibitors of cancer cell migration and invasion from microbial culture filtrates. As a result, we isolated a known compound, ketomycin, from Actinomycetes. DHMEQ, SEMBL, and ketomycin are all NF-κB inhibitors, and inhibited the expression of MMPs in the inhibition of cellular migration and invasion. These are all compounds with comparatively low toxicity, and may be useful for the development of anti-metastasis agents. 相似文献
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15.
Moujalled DM Cook WD Lluis JM Khan NR Ahmed AU Callus BA Vaux DL 《Cell death and differentiation》2012,19(5):808-815
Binding of TNF to TNF receptor-1 can give a pro-survival signal through activation of p65/RelA NF-κB, but also signals cell death. To determine the roles of FLICE-inhibitory protein (FLIP) and caspase-8 in TNF-induced activation of NF-κB and apoptosis, we used mouse embryonic fibroblasts derived from FLIP and caspase-8 gene-deleted mice, and treated them with TNF and a smac-mimetic compound that causes degradation of cellular inhibitor of apoptosis proteins (cIAPs). In cells treated with smac mimetic, TNF and Fas Ligand caused wild-type and FLIP(-/-) MEFs to die, whereas caspase-8(-/-) MEFs survived, indicating that caspase-8 is necessary for death of MEFs triggered by these ligands when IAPs are degraded. By contrast, neither caspase-8 nor FLIP was required for TNF to activate p65/RelA NF-κB, because IκB was degraded, p65 translocated to the nucleus, and an NF-κB reporter gene activated normally in caspase-8(-/-) or FLIP(-/-) MEFs. Reconstitution of FLIP(-/-) MEFs with the FLIP isoforms FLIP-L, FLIP-R, or FLIP-p43 protected these cells from dying when treated with TNF or FasL, whether or not cIAPs were depleted. These results show that in MEFs, caspase-8 is necessary for TNF- and FasL-induced death, and FLIP is needed to prevent it, but neither caspase-8 nor FLIP is required for TNF to activate NF-κB. 相似文献
16.
Marisa Freitas Ana Gomes Graça Porto Eduarda Fernandes 《Journal of biological inorganic chemistry》2010,15(8):1275-1283
Many lines of evidence have suggested that oxidative stress and inflammation play a pivotal role in the toxicity of nickel
salts. Considering that neutrophils are active participants in inflammatory processes, namely by producing high amounts of
reactive oxygen species, the aim of the present study was to evaluate the putative activation of human neutrophils’ oxidative
burst by nickel. Subsequently, the influence of nickel in the pathways leading to NADPH oxidation in neutrophils was evaluated
by measuring protein kinase C (PKC) activation. The effects of nickel on neutrophils’ nuclear factor κB (NF-κB) activation
and on the production of the proinflammatory mediators interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor α were also
evaluated. The results obtained showed that nickel, at concentrations that may be attained in vivo, stimulates the production of superoxide radical (O2
·−), hydrogen peroxide (H2O2), and hypochlorous acid (HOCl) in human neutrophils in vitro, via activation of PKC. In addition, nickel was shown to activate
NF-κB and to induce the production of IL-8 in these cells. These observations indicate that the sustained activation of human
neutrophils by nickel may contribute for the long-term adverse effects on human health mediated by this metal. 相似文献
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The IκB kinase/NF-κB signaling pathway has been implicated in the pathogenesis of several inflammatory diseases. Increased activation of NF-κB is often detected in both immune and non-immune cells in tissues affected by chronic inflammation, where it is believed to exert detrimental functions by inducing the expression of proinflammatory mediators that orchestrate and sustain the inflammatory response and cause tissue damage. Thus, increased NF-κB activation is considered an important pathogenic factor in many acute and chronic inflammatory disorders, raising hopes that NF-κB inhibitors could be effective for the treatment of inflammatory diseases. However, ample evidence has accumulated that NF-κB inhibition can also be harmful for the organism, and in some cases trigger the development of inflammation and disease. These findings suggested that NF-κB signaling has important functions for the maintenance of physiological immune homeostasis and for the prevention of inflammatory diseases in many tissues. This beneficial function of NF-κB has been predominantly observed in epithelial cells, indicating that NF-κB signaling has a particularly important role for the maintenance of immune homeostasis in epithelial tissues. It seems therefore that NF-κB displays two faces in chronic inflammation: on the one hand increased and sustained NF-κB activation induces inflammation and tissue damage, but on the other hand inhibition of NF-κB signaling can also disturb immune homeostasis, triggering inflammation and disease. Here, we discuss the mechanisms that control these apparently opposing functions of NF-κB signaling, focusing particularly on the role of NF-κB in the regulation of immune homeostasis and inflammation in the intestine and the skin. 相似文献