共查询到20条相似文献,搜索用时 0 毫秒
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《FEBS letters》2014,588(8):1315-1321
The role of gap junctions, particularly that of connexin43 (Cx43), has become an area of increasing interest in bone physiology. An abundance of studies have shown that Cx43 influences the function of osteoblasts and osteocytes, which ultimately impacts bone mass acquisition and skeletal homeostasis. However, the molecular details underlying how Cx43 regulates bone are only coming into focus and have proven to be more complex than originally thought. In this review, we focus on the diverse molecular mechanisms by which Cx43 gap junctions and hemichannels regulate cell signaling pathways, gene expression, mechanotransduction and cell survival in bone cells. This review will highlight key signaling factors that have been identified as downstream effectors of Cx43 and the impact of these pathways on distinct osteoblast and osteocyte functions. 相似文献
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《Journal of cellular and molecular medicine》2017,21(7):1315-1328
Podocyte dysfunction results in glomerular diseases accounted for 90% of end‐stage kidney disease. The evolutionarily conserved Notch signalling makes a crucial contribution in podocyte development and function. However, the underlying mechanism of Notch pathway modulating podocyte differentiation remains less obvious. Autophagy, reported to be related with Notch signalling pathways in different animal models, is regarded as a possible participant during podocyte differentiation. Here, we found the dynamic changes of Notch1 were coincided with autophagy: they both increased during kidney development and podocyte differentiation. Intriguingly, when Notch signalling was down‐regulated by DAPT, autophagy was greatly diminished, and differentiation was also impaired. Further, to better understand the relationship between Notch signalling and autophagy in podocyte differentiation, rapamycin was added to enhance autophagy levels in DAPT‐treated cells, and as a result, nephrin was recovered and DAPT‐induced injury was ameliorated. Therefore, we put forward that autophagy is involved in kidney development and podocyte differentiation regulated by Notch signalling. 相似文献
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Hong L Han Y Li S Yang J Gong T Li J Zheng J Zhang H Zhao Q Wu K Fan D 《Cell biology international》2011,35(4):321-324
Here, we have first investigated the roles of ZNRD1 in angiogenesis of leukaemia. The leukaemia cell line K562 was transfected with the vector that included the full-length cDNA of ZNRD1, then the growth and angiogenesis of cells were detected. Up-regulation of ZNRD1 could significantly inhibit the growth of cells, reduce tumour microvessel densities and inhibit the VEGF (vascular endothelial growth factor) production. The results of human miRNA array and real-time PCR showed that ZNRD1 could significantly up-regulate the expression of miR-214 and down-regulate the expression of miR-296. Taken together, ZNRD1 might inhibit tumour angiogenesis and could be considered as a target for leukaemia therapy. 相似文献
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Elena Mariotto Diana Corallo Marcella Pantile Emanuela Giarin Martina Pigazzi Giuseppe Basso Giampietro Viola Sanja Aveic 《Journal of cellular and molecular medicine》2021,25(18):9060-9065
BCL2-associated athanogene-1 (BAG1) is a multi-functional protein that is found deregulated in several solid cancers and in paediatric acute myeloid leukaemia. The investigation of BAG1 isoforms expression and intracellular localization in B-cell acute lymphoblastic leukaemia (B-ALL) patient-derived specimens revealed that BAG1 levels decrease during disease remission, compared to diagnosis, but drastically increase at relapse. In particular, at diagnosis both BAG1-L and BAG1-M isoforms are mainly nuclear, while during remission the localization pattern changes, having BAG1-M almost exclusively in the cytosol indicating its potential cytoprotective role in B-ALL. In addition, knockdown of BAG1/BAG3 induces cell apoptosis and G1-phase cell cycle arrest and, more intriguingly, shapes cell response to chemotherapy. BAG1-depleted cells show an increased sensitivity to the common chemotherapeutic agents, dexamethasone or daunorubicin, and to the BCL2 inhibitor ABT-737. Moreover, the BAG1 inhibitor Thio-2 induces a cytotoxic effect on RS4;11 cells both in vitro and in a zebrafish xenograft model and strongly synergizes with pan-BCL inhibitors. Collectively, these data sustain BAG1 deregulation as a critical event in assuring survival advantage to B-ALL cells. 相似文献
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Enhancement of transient gene expression by fed-batch culture of HEK 293 EBNA1 cells in suspension 总被引:1,自引:0,他引:1
Enhanced green fluorescence protein (GFP) and erythropoietin (EPO) were used as reporters to assess and improve transient
gene expression in HEK 293 EBNA1 cells. The production of EPO only lasted 3 days and reached 18.1 mg/l in suspension cultures
in 1 l batch bioreactors. However, GFP expression examined in well-plate experiments persisted for 12 days in transfected
cells but decreased rapidly within the next 15 days. These results suggest that the retaining of a plasmid in cells may not
be a limiting factor for protein expression in large-scale transient transfection. To improve cell maintenance and protein
expression, a fed-batch culture was performed using an enriched medium, a mixture of equal volumes of 293 SFM II medium and
a 5 × amino acid solution prepared based on DMEM/F12 medium formula. EPO reached 33.6 mg/l, representing 86% increase over
that of the batch culture. Moreover, the total amount of EPO produced was increased by 165% in view of the volume increase
in the fed-batch culture. The serum-free medium used in this work enables cells growing well and transfection without medium
change. Thus, the process reported here is simple and easy to scale up. 相似文献
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Yifeng Dai Zhiheng Cheng Doerte R. Fricke Hongyou Zhao Wenhui Huang Qingfu Zhong Pei Zhu Wenjuan Zhang Zhihua Wu Qing Lin Huoyan Zhu Yan Liu Tingting Qian Lin Fu Longzhen Cui Tiansheng Zeng 《Journal of cellular and molecular medicine》2021,25(3):1456-1467
Wnt-Fzd signalling pathway plays a critical role in acute myeloid leukaemia (AML) progression and oncogenicity. There is no study to investigate the prognostic value of Wnt and Fzd gene families in AML. Our study screened 84 AML patients receiving chemotherapy only and 71 also undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. We found that some Wnt and Fzd genes had significant positive correlations. The expression levels of Fzd gene family were independent of survival in AML patients. In the chemotherapy group, AML patients with high Wnt2B or Wnt11 expression had significantly shorter event-free survival (EFS) and overall survival (OS); high Wnt10A expressers had significantly longer OS than the low expressers (all P < .05), whereas, in the allo-HSCT group, the expression levels of Wnt gene family were independent of survival. We further found that high expression of Wnt10A and Wnt11 had independent prognostic value, and the patients with high Wnt10A and low Wnt11 expression had the longest EFS and OS in the chemotherapy group. Pathway enrichment analysis showed that genes related to Wnt10A, Wnt11 and Wnt 2B were mainly enriched in ‘cell morphogenesis involved in differentiation’, ‘haematopoietic cell lineage’, ‘platelet activation, signalling and aggregation’ and ‘mitochondrial RNA metabolic process’ signalling pathways. Our results indicate that high Wnt2B and Wnt11 expression predict poor prognosis, and high Wnt10A expression predicts favourable prognosis in AML, but their prognostic effects could be neutralized by allo-HSCT. Combined Wnt10A and Wnt11 may be a novel prognostic marker in AML. 相似文献
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Yu‐Chi Li Wei‐Lin Wan Jeng‐Shane Lin Yun‐Wei Kuo Yu‐Chi King Shih‐Tong Jeng 《Plant, cell & environment》2016,39(7):1576-1587
Hydroxyproline‐rich glycopeptides (HypSys) are small signalling peptides containing 18–20 amino acids. The expression of IbpreproHypSys, encoding the precursor of IbHypSys, was induced in sweet potato (Ipomoea batatas cv. Tainung 57) through wounding and IbHypSys treatments by using jasmonate and H2O2. Transgenic sweet potatoes overexpressing (OE) and silencing [RNA interference (RNAi)] IbpreproHypSys were created. The expression of the wound‐inducible gene for ipomoelin (IPO) in the local and systemic leaves of OE plants was stronger than the expression in wild‐type (WT) and RNAi plants after wounding. Furthermore, grafting experiments indicated that IPO expression was considerably higher in WT stocks receiving wounding signals from OE than from RNAi scions. However, wounding WT scions highly induced IPO expression in OE stocks. These results indicated that IbpreproHypSys expression contributed towards sending and receiving the systemic signals that induced IPO expression. Analysing the genes involved in the phenylpropanoid pathway demonstrated that lignin biosynthesis was activated after synthetic IbHypSys treatment. IbpreproHypSys expression in sweet potato suppressed Spodoptera litura growth. In conclusion, wounding induced the expression of IbpreproHypSys, whose protein product was processed into IbHypSys. IbHypSys stimulated IbpreproHypSys and IPO expression and enhanced lignin biosynthesis, thus protecting plants from insects. 相似文献
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Dr Wayne R. Leifert Amanda L. Aloia Olgatina Bucco Edward J. McMurchie 《Molecular membrane biology》2013,30(6):507-517
G-protein coupled receptors (GPCRs) form a ternary complex of agonist, receptor and G-proteins during primary signal transduction at the cell membrane. Downstream signalling is thought to be preceded by the process of dissociation of Gα and Gβγ subunits, thus exposing new surfaces to interact with downstream effectors. We demonstrate here for the first time, the dissociation of heterotrimeric G-protein subunits (i.e., Gα and Gβγ) following agonist-induced GPCR (α2A-adrenergic receptor; α2A-AR) activation in a cell-free assay system. α2A-AR membranes were reconstituted with the G-proteins (±hexahistidine-tagged) Gαi1 and Gβ1γ2 and functional signalling was determined following activation of the reconstituted receptor:G-protein complex with the potent agonist UK-14304, and [35S]GTPγS. In the presence of Ni2+-coated agarose beads, the activated his-tagged Gαi1his-[35S]GTPγS complex was captured on the Ni2+-presenting surface. When his-tagged Gβ1γ2 (Gβ1γ2his) was used with Gαi1, the [35S]GTPγS-bound Gαi1 was not present on the Ni2+-coated beads, but rather, it was separated from the β1γ2(his)-beads, demonstrating receptor-induced dissociation of Gα and Gβγ subunits. Treatment of the reconstituted α2A-AR membranes containing Gβ1γ2his:Gαi1 with imidazole confirmed the specificity for the Ni2+:G-protein surface dissociation of Gαi1 from Gβ1γ2his. These data demonstrate for the first time, the complete dissociation of the G-protein subunits and extend observations on the role of G-proteins in the assembly and disassembly of the ternary complex in the primary events of GPCR signalling. 相似文献
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Differential regulation of signal transduction pathways in wild type and mutated p53 breast cancer epithelial cells by copper and zinc 总被引:5,自引:0,他引:5
Previous studies have suggested that cells may differ in their response to metal stress. This study was undertaken to investigate the role of PI3K/Akt signaling pathway in metal resistance in human breast cancer epithelial cells with different p53 and estrogen receptor status. Exposure to copper and zinc increased Akt phosphorylation with its nuclear localization only in MDA-MB-231 cells with no estrogen receptor and mutated p53. Cyclin D1 expression and cell-cycle progression followed the metal-induced Akt phosphorylation. Treatment with LY294002 abrogated these effects, suggesting the essential role of PI3-kinase. In contrast, in MCF-7 cells with wild type p53 and estrogen receptor, there was no change in Akt activation, while suppression of p53 activity by pifithrin-alpha increased phosphorylation of Akt after the treatment with copper. In MCF-7 cells, the metal treatment increased the phosphorylation of p53 at serine 15, up-regulated p21 expression, and resulted in cell-cycle arrest in G1 phase with apoptosis. These results demonstrate that copper-induced apoptosis in MCF-7 cells is p53 dependent, whereas the metal resistance in MDA-MB-231 cells may be due to activation of Akt in the absence of a functional p53. 相似文献
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Calzavara E Chiaramonte R Cesana D Basile A Sherbet GV Comi P 《Journal of cellular biochemistry》2008,103(5):1405-1412
Notch signalling plays an important role in hematopoiesis and in the pathogenesis of T-ALL. Notch is known to interact with Ras and PTEN/PI3K (phosphoinositide-3 kinase)/Akt pathways. We investigated the interaction of Notch with these pathways and the possible reciprocal regulation of these signalling systems in T-ALL cells in vitro. Our analyses indicate that the PI3K/Akt pathway is constitutively active in the four T-ALL cell lines tested. Akt phosphorylation was not altered by the sequestration of growth factors, that is, Akt activation seems to be less dependent on but not completely independent of growth factors, possibly being not subject to negative feedback regulation. PTEN expression was not detected in 3/4 cell lines tested, suggesting the loss of PTEN-mediated Akt activation. Inhibition of the PI3K/Akt pathway arrests growth and enhances apoptosis, but with no modulation of expression of Bax-alpha and Bcl-2 proteins. We analysed the relationship between Notch-1 and the PI3K/Akt signalling and show that inhibition of the Akt pathway changes Notch expression; Notch-1 protein decreased in all the cell lines upon treatment with the inhibitor. Our studies strongly suggest that Notch signalling interacts with PI3K/Akt signalling and further that this occurs in the absence of PTEN expression. The consequences of this to the signalling outcome are yet unclear, but we have uncovered a significant inverse relationship between Notch and PI3K/Akt pathway, which leads us to postulate the operation of a reciprocal regulatory loop between Notch and Ras-PI3K/Akt in the pathogenesis of T-ALL. 相似文献