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Otsuki T Young DB Sasaki DT Pando MP Li J Manning A Hoekstra M Hoatlin ME Mercurio F Liu JM 《Journal of cellular biochemistry》2002,86(4):613-623
Fanconi anemia (FA), a genetic disorder predisposing to aplastic anemia and cancer, is characterized by hypersensitivity to DNA-damaging agents and oxidative stress. Five of the cloned FA proteins (FANCA, FANCC, FANCE, FANCF, FANCG) appear to be involved in a common functional pathway that is required for the monoubiquitination of a sixth gene product, FANCD2. Here, we report that FANCA associates with the IkappaB kinase (IKK) signalsome via interaction with IKK2. Components of the FANCA complex undergo rapid, stimulus-dependent changes in phosphorylation, which are blocked by kinase-inactive IKK2 (IKK2 K > M). When exposed to mitomycin C, cells expressing IKK2 K > M develop a cell cycle abnormality characteristic of FA. Thus, FANCA may function to recruit IKK2, thus providing the cell a means of rapidly responding to stress. 相似文献
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Stuart A. Newman 《Journal of biosciences》1992,17(3):193-215
Early embryos of metazoan species are subject to the same set of physical forces and interactions as any small parcels of semi-solid material, living or nonliving. It is proposed that such “generic” properties of embryonic tissues have played a major role in the evolution of biological form and pattern by providing an array of morphological templates, during the early stages of metazoan phylogeny, upon which natural selection could act. The generic physical mechanisms considered include sedimentation, diffusion, and reaction-diffusion coupling, all of which can give rise to chemical nonuniformities (including periodic patterns) in eggs and small multicellular aggregates, and differential adhesion, which can lead to the formation of boundaries of non-mixing between adjacent cell populations. Generic mechanisms that produce chemical patterns, acting in concern with the capacity of cells to modulate their adhesivity (presumed to be a primitive, defining property of metazoa), could lead to multilayered gastrulae of various types, segmental organization, and many of the other distinguishing characteristics of extant and extinct metazoan body plans. Similar generic mechanisms, acting on small tissue primordia during and subsequent to the establishment of the major body plans, could have given rise to the forms of organs, such as the vertebrate limbs. Generic physical processes acting on a single system of cells and cell products can often produce a widely divergent set of morphological phenotypes, and these are proposed to be the raw material of the evolution of form. The establishment of any ecologically successful form by these mechanisms will be followed, under this hypothesis, by a period of genetic evolution, in which the recruitment of gene products to produce the “generically templated” morphologies by redundant pathways would be favoured by intense selection, leading to extensive genetic change with little impact on the fossil record. In this view, the stabilizing and reinforcing functions of natural selection are more important than its ability to effect incremental change in morphology. Aspects of evolution which are problematic from the standard neo-Darwinian viewpoint, or not considered within that framework, but which follow in a straightforward fashion from the view presented here, include the beginnings of an understanding of why organisms have the structure and appearance they’ do, why homoplasy (the recurrent evolution of certain forms) is so prevalent, why evolution has the tempo and mode it does (“punctuated equilibrium”), and why a “rapid” burst of morphological evolution occurred so soon after the origin of the metazoa. 相似文献
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Binbin Yu Yan Zhang Kailiu Wu Lizhen Wang Yingying Jiang Wantao Chen Ming Yan 《Journal of cellular and molecular medicine》2019,23(2):954-966
CD147/basigin (BSG) is highly upregulated in many types of cancer, our previous study has found that CD147/BSG is highly expressed in head and neck squamous cell carcinoma (HNSCC) stem cells, but its role in HNSCC and the underlying mechanism is still unknown. In this study, we investigated the role of CD147 in the progression of HNSCC. Real‐time PCR, western blot and immunohistochemistry were used to detect the expression of CD147 in total 189 HNSCC tissues in compared with normal tissues. In addition, we used proliferation, colony formation, cell cycle and apoptosis, migration and invasion as well as wound‐healing assay to determine the biological roles of CD147 in HNSCC. Then, a xenograft model was performed to evaluate tumor‐promoting and metastasis‐promoting role of CD147 in HNSCC. The results showed that upregulated CD147 expression was associated with aggressive clinicopathologic features in HNSCC. In addition, CD147 promoted proliferation, migration and reduced the apoptosis phenotype of HNSCC cells in vitro as well as tumor initiation and progression in vivo. Furthermore, we demonstrated that CD147 promoted HNSCC progression through nuclear factor kappa B signaling. Therefore, we concluded that CD147 promoted tumor progression in HNSCC and might be a potential prognostic and treatment biomarker for HNSCC. 相似文献
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Xiao Ma Albert Sickmann Jessica Pietsch Robert Wildgruber Gerhard Weber Manfred Infanger Johann Bauer Daniela Grimm 《Proteomics》2014,14(6):689-698
Proteomic changes of two types of human endothelial cells (ECs) were determined and compared to morphological alterations occurring during the scaffold‐free in vitro formation of 3D structures resembling vascular intimas. The EA.hy926 cell line and human microvascular ECs (HMVECs) were cultured on a random positioning machine or static on ground (normal gravity) for 5 and 7 days, before their morphology was examined and their protein content was analysed by MS after free‐flow electrophoretic separation. A total of 1175 types of proteins were found in EA.hy926 cells and 846 in HMVEC forming 3D structures faster than the EA.hy926 cells. Five hundred and eighty‐four of these kinds of proteins were present in both types of cells. They included a number of metabolic enzymes, of structure‐related and stress proteins. Comparing proteins of EA.hy926 cells growing either adherently on ground or in 3D aggregates on the random positioning machine revealed that ribosomal proteins were enhanced, while tubes are formed and various components of 26S proteasomes remained prevalent in static normal gravity control cells only. The fast developing tube‐like 3D structures of HMVEC suggested a transient augmentation of ribosomal proteins during the 3D assembling of ECs. 相似文献
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A simulation model of the evolution of a free-living bilayered animal is proposed. The model object developed two layers of cells. The inner layer was able to produce digestive enzymes, to split and absorb organic substances. The evolution of these model objects was accompanied by mutations resembling real adaptations in some coelenterates and placozoans. It was observed that the outer layer of the model produced cells capable of secretion of digestive ferments. This mutation was a principal apomorphy leading to the appearance of organisms with extraorganismal digestion. Visual Basic and STELLA modeling software were used for simulations. 相似文献
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Kai‐You Song Xian‐Zhao Zhang Feng Li Qing‐Rong Ji 《Journal of cellular and molecular medicine》2020,24(8):4466-4479
Myocardial infarction (MI) is an acute coronary syndrome that refers to tissue infarction of the myocardium. This study aimed to investigate the effect of long intergenic non‐protein‐coding RNA (lincRNA) ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1‐AS1) against MI by targeting nuclear factor‐kappa‐B inhibitor alpha (NFKBIA) and mediating the nuclear factor‐kappa‐B (NF‐κB) signalling pathway. An MI mouse model was established and idenepsied by cardiac function evaluation. It was determined that ATP2B1‐AS1 was highly expressed, while NFKBIA was poorly expressed and NF‐κB signalling pathway was activated in MI mice. Cardiomyocytes were extracted from mice and introduced with a series of mouse ATP2B1‐AS1 vector, NFKBIA vector, siRNA‐mouse ATP2B1‐AS1 and siRNA‐NFKBIA. The expression of NF‐κBp50, NF‐κBp65 and IKKβ was determined to idenepsy whether ATP2B1‐AS1 and NFKBIA affect the NF‐κB signalling pathway, the results of which suggested that ATP2B1‐AS1 down‐regulated the expression of NFKBIA and activated the NF‐κB signalling pathway in MI mice. Based on the data from assessment of cell viability, cell cycle, apoptosis and levels of inflammatory cytokines, either silencing of mouse ATP2B1‐AS1 or overexpression of NFKBIA was suggested to result in reduced cardiomyocyte apoptosis and expression of inflammatory cytokines, as well as enhanced cardiomyocyte viability. Our study provided evidence that mouse ATP2B1‐AS1 silencing may have the potency to protect against MI in mice through inhibiting cardiomyocyte apoptosis and inflammation, highlighting a great promise as a novel therapeutic target for MI. 相似文献
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Vincent Kam Wai Wong Hua Zhou Simon Shiu Fai Cheung Ting Li Liang Liu 《Journal of cellular biochemistry》2009,107(2):303-315
Saikosaponin‐d (Ssd) is a triterpene saponin derived from the medicinal plant, Bupleurum falcatum L. (Umbelliferae). Previous findings showed that Ssd exhibits a variety of pharmacological and immunomodulatory activities including anti‐inflammatory, anti‐bacterial, anti‐viral and anti‐cancer effects. In the current study we have investigated the effects of Ssd on activated mouse T lymphocytes through the NF‐κB, NF‐AT and AP‐1 signaling pathways, cytokine secretion, and IL‐2 receptor expression. The results demonstrated that Ssd not only suppressed OKT3/CD28‐costimulated human T cell proliferation, it also inhibited PMA, PMA/Ionomycin and Con A‐induced mouse T cell activation in vitro. The inhibitory effect of Ssd on PMA‐induced T cell activation was associated with down‐regulation of NF‐κB signaling through suppression of IKK and Akt activities. In addition, Ssd suppressed both DNA binding activity and the nuclear translocation of NF‐AT and activator protein 1 (AP‐1) of the PMA/Ionomycin‐stimulated T cells. The cell surface markers like IL‐2 receptor (CD25) were also down‐regulated together with decreased production of pro‐inflammatory cytokines of IL‐6, TNF‐α and IFN‐γ. These results indicate that the NF‐κB, NF‐AT and AP‐1 (c‐Fos) signaling pathways are involved in the T cell inhibition evoked by Ssd, so it can be a potential candidate for further study in treating T cell‐mediated autoimmune conditions. J. Cell. Biochem. 107: 303–315, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
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P19 embryonic carcinoma cells can be differentiated into neurons that form synaptic connections and that produce a variety of neurotransmitters. Results of RT‐PCR indicate that P19 neurons express several neurotrophin receptors (p75NTR, trkB, and trkC, but not trkA) but they do not express any of the four neurotrophins. Consistent with the presence of trkB but not trkA, BDNF causes rapid phosphorylation of MAP kinases ERK1 and ERK2, but NGF does not. Neurotrophins induce translocation of NF‐κB into the nucleus. All four neurotrophins induce activation of NF‐κB in a biphasic manner. This effect is apparently mediated by p75NTR, because an inhibitor of trk receptors, K252a, does not inhibit activation of NF‐κB. Instead, K252a itself promotes activation of NF‐κB and this effect is additive with the effect of neurotrophins. Inhibition of reactive oxygen intermediates with PDTC completely abolishes basal activity of NF‐κB and strongly inhibits activation of NF‐κB by neurotrophins, indicating an important role of reactive oxygen intermediates in the pathway by which neurotrophins activate NF‐κB. NF‐κB is known to promote expression of the iNOS gene. We found that all four neurotrophins increased iNOS mRNA levels, resulting in increased accumulation of iNOS protein. In contrast, none of the neurotrophins stimulated nNOS mRNA or protein synthesis. PDTC abolishes constitutive and neurotrophin‐induced expression of iNOS mRNA and protein and abolishes constitutive expression of nNOS mRNA, suggesting that reactive oxygen intermediates promote expression of nNOS. © 2003 Wiley Periodicals, Inc. J Neurobiol 55: 191–203, 2003 相似文献
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Sha Wei Dianbing Wang Hua Li Lijun Bi Jiaoyu Deng Guofeng Zhu Jibin Zhang Chuanyou Li Min Li Yuan Fang Guimin Zhang Jian Chen Shengce Tao Xian‐En Zhang 《Cellular microbiology》2019,21(12)
Mycobacterium tuberculosis (Mtb) manipulates multiple host defence pathways to survive and persist in host cells. Understanding Mtb–host cell interaction is crucial to develop an efficient means to control the disease. Here, we applied the Mtb proteome chip, through separately interacting with H37Ra and H37Rv stimulated macrophage lysates, screened 283 Mtb differential proteins. Through primary screening, we focused on fatty acylCoA synthetase FadD13. Mtb FadD13 is a potential drug target, but its role in infection remains unclear. Deletion of FadD13 in Mtb reduced the production of proinflammatory cytokines IL‐1β, IL‐18, and IL‐6. Bimolecular fluorescence complementation and colocalization showed that the binding partner of FadD13 in macrophage was eEF1A1 (a translation elongation factor). Knockdown eEF1A1 expression in macrophage abrogated the promotion of proinflammatory cytokines induced by FadD13. In addition, ΔfadD13 mutant decreased the expression of the NF‐κB signalling pathway related proteins p50 and p65, so did the eEF1A1 knockdown macrophage infected with H37Rv. Meanwhile, we found that deletion of FadD13 reduced Mtb survival in macrophages during Mtb infection, and purified FadD13 proteins induced broken of macrophage membrane. Taken together, FadD13 is crucial for Mtb proliferation in macrophages, and it plays a key role in the production of proinflammatory cytokines during Mtb infection. 相似文献
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We previously identified functional N-methyl-D-aspartate (NMDA) glutamate receptors in mature osteoclasts and demonstrated that they are involved in bone resorption in vitro. In the present work, we studied the expression of NMDA receptors (NMDAR) by osteoclast precursors and their role in osteoclastogenesis using two in vitro models, the murine myelomonocytic RAW 264.7 cell line and mouse bone marrow cells, both of which differentiate into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF) and Rank ligand (RankL). Using RT-PCR analysis with specific probes, we showed that RAW 264.7 cells and mouse bone marrow cells express mRNA of NMDAR subunits NMDA receptor 1 (NR1) and NMDA receptor 2 (NR2) A, B, and D. These subunits are expressed all along the differentiation sequence from undifferentiated precursors to mature resorbing osteoclasts. Semi-quantitative PCR analysis showed no regulation of the expression of these subunits during the differentiation process. Two specific non competitive antagonists of NMDAR, MK801 and DEP, dose-dependently inhibited osteoclast formation in both models, indicating that osteoclastogenesis requires the activation of NMDAR expressed by osteoclast precursors. MK801 had no effect when added only during the first 2 days of culture, suggesting that NMDAR are rather involved in the late stages of osteoclast formation. Finally, we demonstrated using Western-blotting and immunofluorescence that activation of NMDAR in RAW 264.7 cells by specific agonists induces nuclear translocation of NF-kappa B, a factor required for osteoclast formation. Altogether, our results indicate that osteoclast precursors express NMDAR that are involved in the osteoclast differentiation process through activation of the NF-kappa B pathway. 相似文献
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The ASPP proteins are apoptosis regulators: ASPP1 and ASPP2 promote, while iASPP inhibits, apoptosis. The mechanism by which these different outcomes are achieved is still unknown. The C‐terminal ankyrin repeats and SH3 domain (ANK‐SH3) mediate the interactions of the ASPP proteins with major apoptosis regulators such as p53, Bcl‐2, and NFκB. The structure of the complex between ASPP2ANK‐SH3 and the core domain of p53 (p53CD) was previously determined. We have recently characterized the individual interactions of ASPP2ANK‐SH3 with Bcl‐2 and NFκB, as well as a regulatory intramolecular interaction with the proline rich domain of ASPP2. Here we compared the ASPP interactions at two levels: ASPP2ANK‐SH3 with different proteins, and different ASPP family members with each protein partner. We found that the binding sites of ASPP2 to p53CD, Bcl‐2, and NFκB are different, yet lie on the same face of ASPP2ANK‐SH3. The intramolecular binding site to the proline rich domain overlaps the three intermolecular binding sites. To reveal the basis of functional diversity in the ASPP family, we compared their protein‐binding domains. A subset of surface‐exposed residues differentiates ASPP1 and ASPP2 from iASPP: ASPP1/2 are more negatively charged in specific residues that contact positively charged residues of p53CD, Bcl‐2, and NFκB. We also found a gain of positive charge at the non‐protein binding face of ASPP1/2, suggesting a role in electrostatic direction towards the negatively charged protein binding face. The electrostatic differences in binding interfaces between the ASPP proteins may be one of the causes for their different function. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
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