共查询到20条相似文献,搜索用时 0 毫秒
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Ran Li Yong Wang Zhaofei Yang Yunling He Tong Zhao Ming Fan Xuan Wang Lingling Zhu Xiaomin Wang 《Cell stress & chaperones》2015,20(3):507-516
Hypoxia is an important factor in regulation of cell behavior both under physiological and pathological conditions. The mechanisms of hypoxia-induced cell death have not been completely elucidated yet. It is well known that Ca2+ is critically related to cell survival. Hypoxia-inducible factor-1α (HIF-1α) is a core regulatory factor during hypoxia, and L-type voltage-dependent Ca2+ channels (L-VDCCs) have been reported to play a critical role in cell survival. This study was conducted to explore the relationship between L-VDCC expression and HIF-1α regulation in PC12 cells under hypoxia. PC12 cells were treated at 20 or 3 % O2 to observe its proliferation and the intracellular calcium concentration. Then, we detected the protein expression of HIF-1α and L-VDCCs subtypes, Cav1.2 and Cav1.3. At last, to verify the relationship between HIF-1α and Cav1.2 and Cav1.3, we got the expression of Cav1.2 and Cav1.3 with Western blot and luciferase report gene assays after PC12 cells were treated by echinomycin, which is an HIF-1α inhibitor. Compared with 20 % O2 (normoxia), 3 % O2 (hypoxia) inhibited cell proliferation, increased the intracellular calcium concentration, and induced protein expression of HIF-1α. The protein expression of two L-VDCCs subtypes expressed in the nervous system, Cav1.2 and Cav1.3, was upregulated by hypoxia and reduced dose dependently by treatment with echinomycin, a HIF-1α inhibitor. Luciferase report gene assays showed that the expression of Cav1.2 and Cav1.3 genes was augmented under 3 % O2. However, echinomycin only slightly and dose dependently decreased expression of the Cav1.2 gene, but not that of the Cav1.3 gene. These data indicated that Cav1.2 might be regulated by HIF-1α as one of its downstream target genes and involved in regulation of PC12 cells death under hypoxia. 相似文献
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Viktor Malec Oana R. Gottschald Shu Li Frank Rose Werner Seeger Jörg Hänze 《Free radical biology & medicine》2010,48(12):1626-1635
Fluctuations in cellular oxygenation causing intermittent hypoxia and oxidative stress affect the regulation of hypoxia-inducible factor (HIF-1) and the nuclear factor erythroid 2-related factor 2 (Nrf2). HIF-1 is primarily induced in hypoxia, whereas Nrf2 is induced in response to oxidative stress. Whereas HIF-1 regulates the expression of genes important for the adaptation of cells to hypoxia, Nrf2 induces antioxidative enzymes such as thioredoxin 1 (Trx1), exerting a cytoprotective role. Here, we investigated the regulation and cross talk of HIF-1α and Nrf2 in intermittent hypoxia in lung adenocarcinoma A549 cells expressing high levels of the NADPH oxidase subunit NOX1. Whereas continuous hypoxia induced only HIF-1α, intermittent hypoxia induced both HIF-1α and Nrf2, including its target Trx1. NOX1 was determined to be crucial for enhanced ROS production in intermittent hypoxia that in turn mediated induction of Nrf2 and Trx1. The regulation of Nrf2 and Trx1 by NOX1 was confirmed by both inhibition of endogenous NOX1 and overexpression of recombinant NOX1 protein. By using a proteasomal inhibitor, NOX1 was demonstrated to activate Nrf2 by protein stabilization. Subsequently, Nrf2-dependent Trx1 induction turned out to enhance HIF-1α signaling in intermittent hypoxia. 相似文献
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Qi Yin Peifeng Jin Xuebin Liu Hua Wei Xiaoming Lin Chuang Chi Yu Liu Chengchao Sun Yingjie Wei 《Molecular biology reports》2011,38(1):9-16
Bone marrow-derived mesenchymal stem cells (BMSCs) have been demonstrated to be a promising cell sources for cardiac regeneration.
Poor survival rate of transplanted BMSCs in infarcted myocardium attenuated its clinical application. It’s reported that stromal-derived
factor-1 (SDF-1) could protect progenitor cells including endothelial progenitor cells and embryonic stem cells from apoptosis.
But little is known whether SDF-1α protein has the same protective effects on BMSCs under conditions of hypoxia and serum
deprivation (hypoxia/SD). In present study, we verified that SDF-1α (0.50–2.0 μg/ml) inhibited hypoxia/SD induced apoptosis
of BMSCs through mitochondrial pathway. After administration of SDF-1α, the loss of mitochondrial membrane potential and cytochrome
c released from mitochondria to cytosol were significantly inhibited, and caspase 3 activity also declined. Furthermore, the
effect of SDF-1α on mitochondrial pathway was neutralized by using PI3K inhibitor (Wortmannin) and ERK1/2 inhibitor (U0126).
Our observations suggested that SDF-1α inhibits hypoxia/SD induced BMSCs apoptosis through PI3K/Akt and ERK1/2 signaling pathways.
These data also imply that the anti-apoptotic effect mediated by SDF-1α may enhance cell survival after cell transplantation. 相似文献
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HS Kwon DR Kim EG Yang YK Park HC Ahn SJ Min DR Ahn 《Bioorganic & medicinal chemistry letters》2012,22(16):5249-5252
Vascular endothelial growth factor (VEGF) plays a pro-angiogenic role in tumor progression. Stabilization of a key regulator termed the hypoxia inducible factor (HIF)-1α under oxygen deficient environment around tumor is known to elicit expression of VEGF through binding to p300. Thus, inhibition of the HIF-1α-p300 interaction would lead to down-regulation of VEGF expression, thereby providing potential cancer therapeutics. Here, we have screened a chemical library against the interaction of the HIF-1α-derived peptide with p300 employing a fluorescence polarization-based assay. We have identified a compound as the most prominent inhibitor against the protein-protein interaction. Further, we have observed suppression of the mRNA level of VEGF upon treatment of HeLa cells with the compound, demonstrating its inhibitory effect at the cellular level. 相似文献
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Weidemann Alexander Breyer Johannes Rehm Margot Eckardt Kai-Uwe Daniel Christoph Cicha Iwona Giehl Klaudia Goppelt-Struebe Margarete 《Cell communication and signaling : CCS》2013,11(1):1-7
Background
Increasing structural and biochemical evidence suggests that post-translational methionine oxidation of proteins is not just a result of cellular damage but may provide the cell with information on the cellular oxidative status. In addition, oxidation of methionine residues in key regulatory proteins, such as calmodulin, does influence cellular homeostasis. Previous findings also indicate that oxidation of methionine residues in signaling molecules may have a role in stress responses since these specific structural modifications can in turn change biological activities of proteins.Findings
Here we use tandem mass spectrometry-based proteomics to show that treatment of Arabidopsis thaliana cells with a non-oxidative signaling molecule, the cell-permeant second messenger analogue, 8-bromo-3,5-cyclic guanosine monophosphate (8-Br-cGMP), results in a time-dependent increase in the content of oxidised methionine residues. Interestingly, the group of proteins affected by cGMP-dependent methionine oxidation is functionally enriched for stress response proteins. Furthermore, we also noted distinct signatures in the frequency of amino acids flanking oxidised and un-oxidised methionine residues on both the C- and N-terminus.Conclusions
Given both a structural and functional bias in methionine oxidation events in response to a signaling molecule, we propose that these are indicative of a specific role of such post-translational modifications in the direct or indirect regulation of cellular responses. The mechanisms that determine the specificity of the modifications remain to be elucidated. 相似文献14.
D. Grube 《Histochemistry and cell biology》1980,69(2):157-160
Summary During immunocytochemical investigations on the presence of opioid peptides in gastrointestinal endocrine cells it was found that a subpopulation of plasma cells located in the lamina propria of the canine colonic mucosa showed immunoreactivities for -endorphin. All immunohistochemical specificity controls proved the specificity of the reaction. Circumstantial evidence suggest, however, that no authentic -endorphin is present within this cell type. Possibly sequence homologies between -endorphin and the amino acid composition of a certain immunoglobulin are responsible for the immunocytochemically specific -endorphin-like immunoreactivity of plasma cells.Supported by a grant from the Deutsche Forschungsgemeinschaft, SFB 87/G 2 相似文献
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Persistently elevated level of TNF-α has been implicated in several inflammatory disorders, however, its autocrine production through TNF-α receptors signaling is poorly understood. Here we report that simultaneous silencing of TNF-receptors, R1 and R2 by DNAzyme or siRNA suppressed TNF-α expression more efficiently than silencing them individually in lipopolysaccharides (LPS) stimulated THP-1 macrophages. Co-silencing of TNF-receptors also inhibited TNF-α induced NF-κB activation to a higher extent. It was further observed that NF-κB inhibitor but not c-Jun N-terminal kinase inhibitor (SP600125) suppressed TNF-α expression. All these results suggest that TNF-α expression is regulated by synergistic signaling of TNF receptors through downstream NF-κB activation. 相似文献
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The aim of this study was to investigate the inhibitory mechanism of pure curcumin on WT1 expression in leukemic K562 cells. Pure curcumin suppressed WT1 expression, independent of effects on protein degradation or WT1 mRNA stability. Chromatin immunoprecipitation and reporter gene assays indicate that pure curcumin treatment attenuates WT1 auto-regulation. Interestingly, PKCα inhibition mimicks the repressive effects of pure curcumin in K562 cells. Conversely, myristoylated PKCα over-expression increased WT1 expression and reversed the inhibitory effect of pure curcumin. Our study indicates that pure curcumin attenuates WT1 auto-regulatory function through inhibition of PKCα signaling in K562 cells. 相似文献
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Hui-Jung Jung Jong-Wook Park Jason S. Lee Byeong-Churl Jang Min-Ho Suh 《Biochemical and biophysical research communications》2009,390(1):71-502
Silibinin is a polyphenolic flavonoid isolated from the milk thistle (Silybum marianum) and is reported to exhibit anticancer properties. Recently, it has been reported that silibinin inhibits hypoxia-inducible factor-1α (HIF-1α) expression in cancer cells. However, the precise mechanism by which silibinin decreases HIF-1 expression is not fully understood. In this study, silibinin inhibited basal and hypoxia induced expression levels of HIF-1α protein in LNCaP and PC-3 prostate cancer cells, while the rate of HIF-1α protein degradation and mRNA levels were not affected. We found that the decrease in HIF-1 protein by silibinin correlated with suppression of de novo synthesis of HIF-1α protein. Silibinin inhibited global protein synthesis coincided with reduction of eIF4F complex formation and induction of phosphorylation of the translation initiation factor 2α (eIF-2α) which can cause inhibition of general protein synthesis. These results suggest that silibinin’s activity to inhibit HIF-1α protein expression is associated with the suppression of global protein translation. 相似文献
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Sundaralingam Premaraj Isabela Souza Thyagaseely Premaraj 《Biochemical and biophysical research communications》2013
Periodontal ligament (PDL) cells convert the orthodontic forces into biological responses by secreting signaling molecules to induce modeling of alveolar bone and tooth movement. Beta-catenin pathway is activated in response to mechanical loading in PDL cells. The upstream signaling pathways activated by mechanical loading resulting in the activation of β-catenin pathway through Wnt-independent mechanism remains to be characterized. We hypothesized that mechanical loading induces activation of β-catenin signaling by mechanisms that dependent on focal adhesion kinase (FAK) and nitric oxide (NO). We found that mechanical or pharmacological activation of β-catenin signaling in PDL cells upregulated the expression of β-catenin target genes. Pre-treatment of PDL cells with FAK inhibitor-14 prior to mechanical loading abolished the mechanical loading-induced phosphorylation of Akt and dephosphorylation of β-catenin. PDL cells pre-treated with NO donor or NO inhibitor and subjected to mechanical loading. Western blot analysis showed that the mechanical loading or pre-treatment with NO donor increased the levels of dephosphorylated β-catenin, pAkt, and pGSK-3β. Pre-treatment with NO inhibitor blocked the mechanical loading-induced phosphorylation of Akt and dephosphorylation of β-catenin. These data indicate that mechanical loading-induced β-catenin stabilization in PDL cells involves phosphorylation of Akt by two parallel pathways requiring FAK and NO. 相似文献
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Angel Jemima Ebenezer Kavya Prasad Sanjana Rajan 《Journal of receptor and signal transduction research》2018,38(3):204-212
Context: Mast cell (MC) activation through H4R releases various inflammatory mediators which are associated with allergic asthma.Objectives: To investigate the siRNA-mediated gene silencing effect of H4R on human mast cells (HMCs) functions and the activation of stress-activated protein kinases (SAPK)/jun amino-terminal kinases (JNK) signaling pathways for the release of ineterleukin-1β (IL-1β) in HMCs.Materials and methods: H4R expression was analyzed by RT-PCR and western blotting in human mast cell line-1 (HMC-1) cells and H4RsiRNA transfected cells. The effect of H4RsiRNA and H4R-antagonist on H4R mediated MC functions such as intracellular Ca2+ release, degranulation, IL-6 and IL-1β release, and the activation SAPK/JNK signaling pathways were studied. HMC-1 cells were stimulated with 10?μM of histamine (His) and 4-methylhistamine (4-MH) and pretreated individually with H4R-antagonist JNJ7777120 (JNJ), histamine H1 receptor (H1R)-antagonist mepyramine, and signaling molecule inhibitors SP600125 (SP) and Bay117082.Results: We found that the HMC-1 cells expressed H4R and H4RsiRNA treatment down regulated the H4R expression in HMC-1 cells. Both His and 4-MH induced the intracellular Ca2+ release and degranulation whereas; H4R siRNA and JNJ inhibited the effect. Furthermore, the activation of H4R caused the phosphorylation of SAPK/JNK pathways. H4R gene silencing and pretreatment with SP and JNJ decreased His and 4-MH induced phosphorylation of SAPK/JNK. We found that the activation of H4R caused the release of IL-1β (124.22?pg/ml) and IL-6 (122.50?pg/ml) on HMC-1 cells. Whereas, SAPK/JNK inhibitor (68.36?pg/ml) inhibited the H4R mediated IL-1β release.Conclusions: Taken together, the silencing of H4R inhibited the H4R mediated MC functions and SAPK/JNK phosphorylation. Furthermore, the H4R activation utilized SAPK/JNK signaling pathway for IL-1β release in HMC-1 cells. 相似文献
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David M Patrick Amanda K Leone Jeffry J Shellenberger Kara A Dudowicz Jonathan M King 《BMC physiology》2006,6(1):2-15