共查询到20条相似文献,搜索用时 31 毫秒
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Yutaka Koyama Mio Hayashi Ryuji Nagae Shogo Tokuyama Tomohiro Konishi 《Journal of neurochemistry》2014,130(6):759-769
Expressions of vascular endothelial growth factor (VEGF) receptors in astrocytes are increased in damaged brains. To clarify the regulatory mechanisms of VEGF receptors, the effects of endothelin‐1 (ET‐1) were examined in rat cultured astrocytes. Expressions of VEGF‐R1 and ‐R2 receptor mRNA were at similar levels, whereas the mRNA expressions of VEGF‐R3 and Tie‐2, a receptor for angiopoietins, were lower. Placenta growth factor, a selective agonist of the VEGF‐R1 receptor, induced phosphorylation of focal adhesion kinase (FAK) and extracellular signal regulated kinase 1/2 (ERK1/2). Phosphorylations of FAK and ERK 1/2 were also stimulated by VEGF‐E, a selective VEGF‐R2 agonist. Increased phosphorylations of FAK and ERK1/2 by VEGF165 were reduced by selective antagonists for VEGF‐R1 and ‐R2. Treatment with ET‐1 increased VEGF‐R1 mRNA and protein levels. The effects of ET‐1 on VEGF‐R1 mRNA were mimicked by Ala1,3,11,15‐ET‐1, a selective agonist for ETB receptors, and inhibited by BQ788, an ETB antagonist. ET‐1 did not affect the mRNA levels of VEGF‐R2, ‐R3, and Tie‐2. Pre‐treatment with ET‐1 potentiated the effects of placenta growth factor on phosphorylations of FAK and ERK1/2. These findings suggest that ET‐1 induces up‐regulation of VEGF‐R1 receptors in astrocytes, and potentiates VEGF signals in damaged nerve tissues.
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David A. Davis Garnik Akopian John P. Walsh Constantinos Sioutas Todd E. Morgan Caleb E. Finch 《Journal of neurochemistry》2013,127(4):509-519
Airborne particulate matter (PM) from urban vehicular aerosols altered glutamate receptor functions and induced glial inflammatory responses in rodent models after chronic exposure. Potential neurotoxic mechanisms were analyzed in vitro. In hippocampal slices, 2 h exposure to aqueous nanosized PM (nPM) selectively altered post‐synaptic proteins in cornu ammonis area 1 (CA1) neurons: increased GluA1, GluN2A, and GluN2B, but not GluA2, GluN1, or mGlur5; increased post synaptic density 95 and spinophilin, but not synaptophysin, while dentate gyrus (DG) neurons were unresponsive. In hippocampal slices and neurons, MitoSOX red fluorescence was increased by nPM, implying free radical production. Specifically, N? production by slices was increased within 15 min of exposure to nPM with dose dependence, 1–10 μg/mL. Correspondingly, CA1 neurons exhibited increased nitrosylation of the GluN2A receptor and dephosphorylation of GluN2B (S1303) and of GluA1 (S831 & S845). Again, DG neurons were unresponsive to nPM. The induction of N? and nitrosylation were inhibited by AP5, an NMDA receptor antagonist, which also protects neurite outgrowth in vitro from inhibition by nPM. Membrane injury (EthidiumD‐1 uptake) showed parallel specificity. Finally, nPM decreased evoked excitatory post‐synaptic currents of CA1 neurons. These findings further document the selective impact of nPM on glutamatergic functions and identify novel responses of NMDA receptor‐stimulated N? production and nitrosylation reactions during nPM‐mediated neurotoxicity.
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Tuftsin (Thr‐Lys‐Pro‐Arg) is a natural immunomodulating peptide found to stimulate phagocytosis in macrophages/microglia. Tuftsin binds to the receptor neuropilin‐1 (Nrp1) on the surface of cells. Nrp1 is a single‐pass transmembrane protein, but its intracellular C‐terminal domain is too small to signal independently. Instead, it associates with a variety of coreceptors. Despite its long history, the pathway through which tuftsin signals has not been described. To investigate this question, we employed various inhibitors to Nrp1's coreceptors to determine which route is responsible for tuftsin signaling. We use the inhibitor EG00229, which prevents tuftsin binding to Nrp1 on the surface of microglia and reverses the anti‐inflammatory M2 shift induced by tuftsin. Furthermore, we demonstrate that blockade of transforming growth factor beta (TGFβ) signaling via TβR1 disrupts the M2 shift similar to EG00229. We report that tuftsin promotes Smad3 phosphorylation and reduces Akt phosphorylation. Taken together, our data show that tuftsin signals through Nrp1 and the canonical TGFβ signaling pathway.
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Veronica Murta Priscila Schilrreff Gerardo Rosciszewski Maria Jose Morilla Alberto Javier Ramos 《Journal of neurochemistry》2018,144(6):748-760
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Metabolomic comparison between cells over‐expressing isocitrate dehydrogenase 1 and 2 mutants and the effects of an inhibitor on the metabolism 下载免费PDF全文
He Wen Hye Rim Cho Taeho Yun Hyeonjin Kim Chul‐Kee Park Se‐Hoon Lee Seung Hong Choi Sunghyouk Park 《Journal of neurochemistry》2015,132(2):183-193
The R132H and R172K mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have neomorphic activity of generating 2‐hydroxyglutarate (2‐HG) which has been implicated in the oncogenesis. Although similarities in structure and enzyme activity for the two isotypic mutations have been suggested, the difference in their cellular localization and biochemical properties suggests differential effects on the metabolic oncogenesis. Using U87 cells transfected with either wild‐type (WT) and mutant (MT) IDH genes, the MT‐IDH1 and MT‐IDH2 cells were compared with NMR‐based metabolomics. When normalized with the respective WT‐IDH cells, the general metabolic shifts of MT‐IDH1 and IDH2 were almost opposite. Subsequent analysis with LC‐MS and metabolic pathway mapping showed that key metabolites in pentose phosphate pathway and tricarboxylic acid cycle are disproportionately altered in the two mutants, suggesting different activities in the key metabolic pathways. Notably, lactate level was lower in MT‐IDH2 cells which produced more 2‐HG than MT‐IDH1 cells, indicating that the Warburg effects can be overridden by the production of 2‐HG. We also found that the effect of a mutant enzyme inhibitor is mainly reduction of the 2‐HG level rather than general metabolic normalization. Overall, the metabolic alterations in the MT‐IDH1 and 2 can be different and seem to be commensurate with the degree of 2‐HG production.
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CK2‐regulated schwannomin‐interacting protein IQCJ‐SCHIP‐1 association with AnkG contributes to the maintenance of the axon initial segment 下载免费PDF全文
Marie‐Jeanne Papandréou Hélène Vacher Marie‐Pierre Fache Esther Klingler Fanny Rueda‐Boroni Géraldine Ferracci Claire Debarnot Christelle Pipéroglou Gontzal Garcia Del Caño Laurence Goutebroze Bénédicte Dargent 《Journal of neurochemistry》2015,134(3):527-537
The axon initial segment (AIS) plays a central role in electrogenesis and in the maintenance of neuronal polarity. Its molecular organization is dependent on the scaffolding protein ankyrin (Ank) G and is regulated by kinases. For example, the phosphorylation of voltage‐gated sodium channels by the protein kinase CK2 regulates their interaction with AnkG and, consequently, their accumulation at the AIS. We previously showed that IQ motif containing J‐Schwannomin‐Interacting Protein 1 (IQCJ‐SCHIP‐1), an isoform of the SCHIP‐1, accumulated at the AIS in vivo. Here, we analyzed the molecular mechanisms involved in IQCJ‐SCHIP‐1‐specific axonal location. We showed that IQCJ‐SCHIP‐1 accumulation in the AIS of cultured hippocampal neurons depended on AnkG expression. Pull‐down assays and surface plasmon resonance analysis demonstrated that AnkG binds to CK2‐phosphorylated IQCJ‐SCHIP‐1 but not to the non‐phosphorylated protein. Surface plasmon resonance approaches using IQCJ‐SCHIP‐1, SCHIP‐1a, another SCHIP‐1 isoform, and their C‐terminus tail mutants revealed that a segment including multiple CK2‐phosphorylatable sites was directly involved in the interaction with AnkG. Pharmacological inhibition of CK2 diminished both IQCJ‐SCHIP‐1 and AnkG accumulation in the AIS. Silencing SCHIP‐1 expression reduced AnkG cluster at the AIS. Finally, over‐expression of IQCJ‐SCHIP‐1 decreased AnkG concentration at the AIS, whereas a mutant deleted of the CK2‐regulated AnkG interaction site did not. Our study reveals that CK2‐regulated IQJC‐SCHIP‐1 association with AnkG contributes to AIS maintenance.
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Hippocampal nuclear factor kappa B accounts for stress‐induced anxiety behaviors via enhancing neuronal nitric oxide synthase (nNOS)‐carboxy‐terminal PDZ ligand of nNOS‐Dexras1 coupling 下载免费PDF全文
Li‐Juan Zhu Huan‐Yu Ni Rong Chen Lei Chang Hu‐Jiang Shi Dan Qiu Zhan Zhang Dan‐Lian Wu Zhao‐Chun Jiang Hong‐Liang Xin Qi‐Gang Zhou Dong‐Ya Zhu 《Journal of neurochemistry》2018,146(5):598-612
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Single cocaine exposure does not alter striatal pre‐synaptic dopamine function in mice: an [18F]‐FDOPA PET study 下载免费PDF全文
David R Bonsall Michelle Kokkinou Mattia Veronese Christopher Coello Lisa A. Wells Oliver D. Howes 《Journal of neurochemistry》2017,143(5):551-560
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Cocaine‐ and amphetamine‐regulated transcript peptide in the nucleus accumbens shell inhibits cocaine‐induced locomotor sensitization to transient over‐expression of α‐Ca2+/calmodulin‐dependent protein kinase II 下载免费PDF全文
Lixia Xiong Qing Meng Xi Sun Xiangtong Lu Qiang Fu Qinghua Peng Jianhua Yang Ki‐Wan Oh Zhenzhen Hu 《Journal of neurochemistry》2018,146(3):289-303
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Caveolin‐1 mediates tissue plasminogen activator‐induced MMP‐9 up‐regulation in cultured brain microvascular endothelial cells 下载免费PDF全文
Thrombolysis with tissue plasminogen activator (tPA) increases matrix metalloproteinase‐9 (MMP‐9) activity in the ischemic brain, which exacerbates blood‐brain barrier injury and increases the risk of symptomatic cerebral hemorrhage. The mechanism through which tPA enhances MMP‐9 activity is not well understood. Here we report an important role of caveolin‐1 in mediating tPA‐induced MMP‐9 synthesis. Brain microvascular endothelial cell line bEnd3 cells were incubated with 5 or 20 μg/ml tPA for 24 hrs before analyzing MMP‐9 levels in the conditioned media and cellular extracts by gelatin zymography. tPA at a dose of 20 μg/mL tPA, but not 5 μg/mL, significantly increased MMP‐9 level in cultured media while decreasing it in cellular extracts. Concurrently, tPA treatment induced a 2.3‐fold increase of caveolin‐1 protein levels in endothelial cells. Interestingly, knockdown of Cav‐1 with siRNA inhibited tPA‐induced MMP‐9 mRNA up‐regulation and MMP‐9 increase in the conditioned media, but did not affect MMP‐9 decrease in cellular extracts. These results suggest that caveolin‐1 critically contributes to tPA‐mediated MMP‐9 up‐regulation, but may not facilitate MMP‐9 secretion in endothelial cells.
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Danielle N. Doll Stephanie L. Rellick Taura L. Barr Xuefang Ren James W. Simpkins 《Journal of neurochemistry》2015,132(4):443-451
Tumor necrosis factor alpha (TNF‐α) is known to exacerbate ischemic brain injury; however, the mechanism is unknown. Previous studies have evaluated the effects of TNF‐α on neurons with long exposures to high doses of TNF‐α, which is not pathophysiologically relevant. We characterized the rapid effects of TNF‐α on basal respiration, ATP production, and maximal respiration using pathophysiologically relevant, post‐stroke concentrations of TNF‐α. We observed a reduction in mitochondrial function as early as 1.5 h after exposure to low doses of TNF‐α, followed by a decrease in cell viability in HT‐22 cells and primary neurons. Subsequently, we used the HT‐22 cell line to determine the mechanism by which TNF‐α causes a rapid and profound reduction in mitochondrial function. Pre‐treating with TNF‐R1 antibody, but not TNF‐R2 antibody, ameliorated the neurotoxic effects of TNF‐α, indicating that TNF‐α exerts its neurotoxic effects through TNF‐R1. We observed an increase in caspase 8 activity and a decrease in mitochondrial membrane potential after exposure to TNF‐α which resulted in a release of cytochrome c from the mitochondria into the cytosol. These novel findings indicate for the first time that an acute exposure to pathophysiologically relevant concentrations of TNF‐α has neurotoxic effects mediated by a rapid impairment of mitochondrial function.
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Fastigial nucleus stimulation regulates neuroprotection via induction of a novel microRNA,rno‐miR‐676‐1, in middle cerebral artery occlusion rats 下载免费PDF全文
Xiao‐Min Pang Jing‐Li Liu Jin‐Pin Li Li‐Gang Huang Lei Zhang Hui‐Yao Xiang Ling‐Bo Feng Chun‐Yong Chen Sheng‐Hua Li Sheng‐You Su 《Journal of neurochemistry》2015,133(6):926-934
Previous studies have shown that fastigial nucleus stimulation (FNS) reduces tissue damage resulting from focal cerebral ischemia. Although the mechanisms of neuroprotection induced by FNS are not entirely understood, important data have been presented in the past two decades. MicroRNAs (miRNAs) are a newly discovered group of non‐coding small RNA molecules that negatively regulate target gene expression and are involved in the regulation of cell proliferation and cell apoptosis. To date, no studies have demonstrated whether miRNAs can serve as mediators of the brain's response to FNS, which leads to endogenous neuroprotection. Therefore, this study investigated the profiles of FNS‐mediated miRNAs. Using a combination of deep sequencing and microarray with computational analysis, we identified a novel miRNA in the rat ischemic cortex after 1 h of FNS. This novel miRNA (PC‐3p‐3469_406), herein referred to as rno‐miR‐676‐1, was upregulated in rats with cerebral ischemia after FNS. In vivo observations indicate that this novel miRNA may have antiapoptotic effects and contribute to neuroprotection induced by FNS. Our study provides a better understanding of neuroprotection induced by FNS.
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Cyclophilin D regulates neuronal activity‐induced filopodiagenesis by fine‐tuning dendritic mitochondrial calcium dynamics 下载免费PDF全文
Shaomei Sui Jing Tian Esha Gauba Qi Wang Lan Guo Heng Du 《Journal of neurochemistry》2018,146(4):403-415
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Yuval Nash Eran Schmukler Dorit Trudler Ronit Pinkas‐Kramarski Dan Frenkel 《Journal of neurochemistry》2017,143(5):584-594
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Kinetic modeling of [18F]VAT,a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non‐human primate brain 下载免费PDF全文
Hongjun Jin Xuyi Yue Hui Liu Junbin Han Hubert Flores Yi Su Stanley M. Parsons Joel S. Perlmutter Zhude Tu 《Journal of neurochemistry》2018,144(6):791-804
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