Journal of Neurochemistry (J NEUROCHEM )

Publisher: International Society for Neurochemistry, Blackwell Publishing

Description

The Journal of Neurochemistry is the leading source for current research worldwide on the molecular chemical and cellular biology of the nervous system. Each issue contains dozens of full-length presentations of significant original findings written by investigators at leading medical and research institutions around the world. The Journal of Neurochemistry is devoted to the prompt publication of high-quality original findings in areas relevant to molecular chemical and cell biological aspects of the nervous system. Papers that are wholly pharmalogical histochemical or immunological and methods papers or the cloning of confirmatory sequences that do not advance knowledge in neurochemistry are not normally considered. The Journal particularly encourages submissions in the areas of molecular and cellular biology. A highlight of each issue is the Journal's critically acclaimed Rapid Communications section presenting new ideas and data of particular importance and timeliness. The Journal's Mini-Reviews present concise self-contained summaries of current research in particularly important areas.

  • Impact factor
    3.97
    Show impact factor history
     
    Impact factor
  • 5-year impact
    4.25
  • Cited half-life
    8.50
  • Immediacy index
    1.13
  • Eigenfactor
    0.07
  • Article influence
    1.30
  • Website
    Journal of Neurochemistry website
  • Other titles
    Journal of neurochemistry, JNC
  • ISSN
    0022-3042
  • OCLC
    1782775
  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publisher details

Blackwell Publishing

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • Some journals impose embargoes typically of 6 or 12 months, occasionally of 24 months
    • no listing of affected journals available as yet
  • Conditions
    • See Wiley-Blackwell entry for articles after February 2007
    • Publisher version cannot be used
    • On author or institutional or subject-based server
    • Server must be non-commercial
    • Publisher copyright and source must be acknowledged with set statement ("The definitive version is available at www.blackwell-synergy.com ")
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'Blackwell Publishing' is an imprint of 'Wiley-Blackwell'
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Glucose is the main energy substrate for neurons, and ketone bodies are known to be alternative substrates. However, the capacity of ketone bodies to support different neuronal functions is still unknown. Thus, a change in energy substrate from glucose alone to a combination of glucose and β-hydroxybutyrate might change neuronal function as there is a known coupling between metabolism and neurotransmission. The purpose of this study was to shed light on the effects of the ketone body β-hydroxybutyrate on glycolysis and neurotransmission in cultured murine glutamatergic neurons. Previous studies have shown an effect of β-hydroxybutyrate on glucose metabolism, and the present study further specified this by showing attenuation of glycolysis when β-hydroxybutyrate was present in these neurons. In addition, the NMDA receptor-induced calcium responses in the neurons were diminished in the presence of β-hydroxybutyrate, whereas a direct effect of the ketone body on transmitter release was absent. However, the presence of β-hydroxybutyrate augmented transmitter release induced by the KATP channel blocker glibenclamide, thus giving an indirect indication of the involvement of KATP channels in the effects of ketone bodies on transmitter release. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 10/2014;
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    ABSTRACT: Ceftriaxone(Cef) selectively increases expression of glial glutamate transporter-1 (GLT-1), which was thought to be neuroprotective in some circumstances. However, the effect of Cef on glutamate uptake of GLT-1 was assayed using in vitro studies such as primary neuron/astrocyte cultures or brain slices. In addition, the effect of Cef on neurons in different ischemic models was still discrepant. Therefore, the present study was undertaken to observe the effect of Cef on neurons in global brain ischemia in rats, and especially to provide direct evidence of the upregulation of GLT-1 uptake for glutamate contributing to the neuronal protection of Cef against brain ischemia. Neuropathological evaluation indicated administration of Cef, especially pre-treatment protocols, significantly prevented delayed neuronal death in hippocampal CA1 subregion normally induced by global brain ischemia. Simultaneously, pre-administration of Cef significantly upregulated the expression of GLT-1. Particularly, GLT-1 uptake assay with (3) H-glutamate in living cells from adult rats showed that upregulation in glutamate uptake accompanied upregulated GLT-1 expression. Inhibition of GLT-1 by antisense oligodeoxynucleotides or dihydrokainate significantly inhibited the Cef-induced upregulation in GLT-1 uptake and the neuroprotective effect against global ischemia. Thus, we may conclude that Cef protects neurons against global brain ischemia via upregulation of the expression and glutamate uptake of GLT-1. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 09/2014;
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    ABSTRACT: Hyperglycemia is known to induce microvascular complications, thereby altering blood-brain barrier (BBB) permeability. The present study investigated the role of matrix metalloproteinases (MMPs) and their endogenous inhibitors in increased BBB permeability and evaluated the protective effect of S-nitrosoglutathione (GSNO) in diabetes. Diabetes was induced in mice by intraperitoneal injection of streptozotocin (40mg/kg body weight) for 5 days and GSNO was administered orally (100μg/kg body weight) daily for 8 weeks after the induction of diabetes. A significant decline in cognitive functions was observed in diabetic mice assessed by Morris water maze test. Increased permeability to different molecular size tracers accompanied by edema and ion imbalance was observed in cortex and hippocampus of diabetic mice. Furthermore, activity of both pro and active-MMP-9 were found to be significantly elevated in diabetic animals. Increased in situ gelatinase activity was observed in tissue sections and isolated microvessels from diabetic mice brain. The increase in activity of MMP-9 was attributed to increased mRNA and protein expression in diabetic mice. In addition, a significant decrease in mRNA and protein expression of tissue inhibitor of matrix metalloproteinase (TIMP-1) was also observed in diabetic animals. However, GSNO supplementation to diabetic animals was able to abridge MMP-9 activation as well as TIMP-1 levels, restoring BBB integrity and also improving learning and memory. Our findings clearly suggest that GSNO could prevent hyperglycemia-induced disruption of BBB by suppressing MMP-9 activity. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 09/2014;
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    Journal of Neurochemistry 08/2014;
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    Journal of Neurochemistry 08/2014;
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    ABSTRACT: Drugs of abuse modulate the function and activity of the mesolimbic dopamine circuit. To identify novel mediators of drug-induced neuroadaptations in the ventral tegmental area (VTA), we performed RNA sequencing analysis on VTA samples from mice administered repeated saline, morphine, or cocaine injections. One gene that was similarly upregulated by both drugs was serum- and glucocorticoid-inducible kinase 1 (SGK1). SGK1 activity, as measured by phosphorylation of its substrate N-myc downstream-regulated gene (NDRG), was also increased robustly by chronic drug treatment. Increased NDRG phosphorylation was evident 1 but not 24 hours after the last drug injection. SGK1 phosphorylation itself was similarly modulated. To determine the role of increased SGK1 activity on drug-related behaviors, we overexpressed constitutively-active (CA) SGK1 in the VTA. SGK1-CA expression reduced locomotor sensitization elicited by repeated cocaine, but surprisingly had the opposite effect and promoted locomotor sensitization to morphine, without affecting the initial locomotor responses to either drug. SGK1-CA expression did not significantly affect morphine or cocaine conditioned place preference (CPP), although there was a trend towards increased CPP with both drugs. Further characterizing the role of this kinase in drug-induced changes in VTA may lead to improved understanding of neuroadaptations critical to drug dependence and addiction. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 08/2014;
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    ABSTRACT: Although the causes of psychiatric disorders are not fully understood, it is well established that mental illness originates from the interaction between genetic and environmental factors. In this regard, compelling evidence demonstrates that depression can be the consequence of altered, and often maladaptive, response to adversities during pre- and early post-natal life. In this study, we investigated the impact of chronic maternal separation on the expression of the neurotrophin brain-derived neurotrophic factor (BDNF) in serotonin transporter knockout rats in the ventral and dorsal hippocampus as well as the ventromedial and dorsomedial prefrontal cortex. We found that both SERT deletion and the maternal separation led to an overall reduction of Bdnf expression in the ventral hippocampus and the ventromedial prefrontal cortex, whereas in the dorsal hippocampus and in the dorsomedial prefrontal cortex we observed a significant increase in the neurotrophin gene expression after MS exposure, specifically in the heterozygous SERT rats. In summary, we show that the modulation of Bdnf expression in SERT mutant rats exposed to maternal separation reflects the complex functional consequences of this gene-environment interaction with a clear distinction between the ventral and the dorsal subfields of the hippocampus and of the prefrontal cortex. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 08/2014;
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    ABSTRACT: During neuronal differentiation, axonal elongation is regulated by both external and intrinsic stimuli, including neurotropic factors, cytoskeleton dynamics, second messengers such as cyclic adenosine monophosphate (cAMP), and neuronal excitability. Chloride intracellular channel 1 (CLIC1) is a cytoplasmic hydrophilic protein that, upon stimulation, dimerizes and translocates to the plasma membrane, where it contributes to increase the membrane chloride conductance. Here, we investigated the expression of CLIC1 in primary hippocampal neurons and retinal ganglion cells (RGCs) and examined how the functional expression of CLIC1 specifically modulates neurite outgrowth of neonatal murine RGCs. Using a combination of electrophysiology and immunohistochemistry, we found that CLIC1 is expressed in hippocampal neurons and RGCs and that the chloride current mediated by CLIC1 is required for maintaining growth cone morphology and sustaining cAMP-stimulated neurite elongation in dissociated immuno-purified RGCs. In cultured RGCs, inhibition of CLIC1 ionic current through the pharmacological blocker IAA94 or a specific anti-CLIC1 antibody directed against its extracellular domain prevent the neurite outgrowth induced by cAMP. CLIC1-mediated chloride current, which results from an increased open probability of the channel, is detected only when cAMP is elevated. Inhibition of protein kinase A (PKA) prevents such current. These results indicate that CLIC1 functional expression is regulated by cAMP via PKA and is required for neurite outgrowth modulation during neuronal differentiation. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 07/2014;
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    ABSTRACT: Neuroinflammation is a feedback mechanism against infection, with recent studies suggesting a neuromodulatory role. The chemokine, C-C chemokine ligand 2 (CCL2), and its receptor, C-C chemokine receptor type 2 (CCR2), affect neuromodulation and migration in response to damage. Although CCL2 co-localizes with neuropeptides in the hypothalamus that control voluntary behavior, the unction of CCL2/CCR2 is unknown. This led us to consider the possibility that CCL2 acting through CCR2, under natural conditions, may affect the migration and peptide levels of hypothalamic neurons that control voluntary behavior. This study used primary embryonic hypothalamic neurons to examine the effect of CCL2 on migratory behavior and on levels of the peptides, enkephalin (ENK) and galanin (GAL). Treatment with CCL2 led to a significant, dose-dependent increase in the number of migrated neurons and an increase in the velocity and distance traveled. CCL2 also significantly increased the number of ENK-expressing and CCR2/ENK co-expressing neurons and the percentage of neurons that contain higher levels of ENK. Lastly, CCL2 produced a dose-dependent increase in expression of ENK and GAL. These results provide evidence for a stimulatory effect of CCL2 on embryonic hypothalamic neurons involving changes in migratory behavior, expression, and synthesis of neuropeptides that function in controlling behavior. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 07/2014;
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    ABSTRACT: The positron emitting (PET) (11) C-labeled Pittsburgh Compound B (PIB) ligand is used to image β-amyloid (Aβ) deposits in the brains of living subjects with the intent of detecting early stages of Alzheimer's disease (AD). However, deposits of human-sequence Aβ in APP transgenic mice and nonhuman primates bind very little PIB. The high stoichiometry of PIB:Aβ binding in human AD suggests that the PIB binding site may represent a particularly pathogenic entity and/or report local pathologic conditions. In this study, (3) H-PIB was employed to track purification of the PIB binding site in > 90% yield from frontal cortical tissue of autopsy-diagnosed AD subjects. The purified PIB binding site comprises a distinct, highly insoluble subfraction of the Aβ in AD brain with low buoyant density due to an SDS-resistant association with a limited subset of brain proteins and lipids with physical properties similar to lipid rafts and to a ganglioside:Aβ complex in AD and Down Syndrome brain. Both the protein and lipid components are required for PIB binding. Elucidation of human-specific biological components and pathways will be important in guiding improvement of the animal models of AD and in identifying new potential therapeutic avenues. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 07/2014;
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    ABSTRACT: The central process in energy production is the oxidation of acetyl-CoA to CO2 by the tricarboxylic acid (TCA, Krebs, citric acid) cycle. However, this cycle functions also as a biosynthetic pathway from which intermediates leave to be converted primarily to glutamate, GABA, glutamine and aspartate and to a smaller extent to glucose derivatives and fatty acids in brain. When TCA cycle ketoacids are removed they must be replaced to permit the continued function of this essential pathway, by a process termed anaplerosis. Since the TCA cycle cannot act as a carbon sink, anaplerosis must be coupled with cataplerosis; the exit of intermediates from the TCA cycle. The role of anaplerotic reactions for cellular metabolism in brain has been studied extensively. However, the coupling of this process with cataplerosis and the roles that both pathways play in the regulation of amino acid, glucose, and fatty acid homeostasis have not been emphasized. The concept of a linkage between anaplerosis and cataplerosis should be underscored, because the balance between these two processes is essential. The hypothesis that cataplerosis in brain is achieved by exporting lactate generated from TCA cycle intermediates into the blood and perivascular area, is presented. This shifts the generally accepted paradigm of lactate generation as simply derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis (AG). This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 07/2014;
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    ABSTRACT: Amphetamine is a central nervous system psychostimulant with a high potential for abuse. Recent literature has shown that genetic and drug-induced elevations in dopamine transporter (DAT) expression augment the neurochemical and behavioral potency of psychostimulant releasers. However, it remains to be determined if the well-documented differences in DAT levels across striatal regions drive regionally distinct AMPH effects within individuals. DAT levels and dopamine uptake rates have been shown to follow a gradient in the striatum, with the highest levels in the dorsal regions and lowest levels in the nucleus accumbens shell; thus, we hypothesized that amphetamine potency would follow this gradient. Using fast scan cyclic voltammetry in mouse brain slices we examined DAT inhibition and changes in exocytotic dopamine release by amphetamine across four striatal regions (dorsal and ventral caudate-putamen, nucleus accumbens core and shell). Consistent with our hypothesis, amphetamine effects at the DAT and on release decreased across regions from dorsal to ventral, and both measures of potency were highly correlated with dopamine uptake rates. Separate striatal subregions are involved in different aspects of motivated behaviors, such as goal-directed and habitual responding, that become dysregulated by drug abuse, making it critically important to understand regional differences in drug potencies. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 07/2014;
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    ABSTRACT: The discoveries of mutations in SNCA were seminal findings that resulted in the knowledge that α-synuclein is the major component of Parkinson's disease-associated Lewy bodies. Since the pathologic roles of these protein inclusions and SNCA mutations are not completely established, we characterized the aggregation properties of the recently identified SNCA mutations, H50Q and G51D, to provide novel insights. The properties of recombinant H50Q, G51D and wild-type α-synuclein to polymerize and aggregate into amyloid were studied using K114 fluorometry, sedimentation analyses, electron microscopy and atomic force microscopy. These studies showed that the H50Q mutation increases the rate of α-synuclein aggregation while the G51D mutation has the opposite effect. However, H50Q and G51D α-synuclein could still be similarly induced to form intracellular aggregates from the exposure to exogenous amyloidogenic seeds under conditions that promote their cellular entry. Both mutant α-synuclein proteins, but especially G51D, promoted cellular toxicity under cellular stress conditions. These findings reveal that the novel pathogenic SNCA mutations, H50Q and G51D, have divergent effects on aggregation properties relative to the wild type protein, with G51D α-synuclein demonstrating reduced aggregation despite presenting with earlier disease, suggesting that these mutants promote different mechanisms of α-synuclein pathogenesis. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 07/2014;
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    ABSTRACT: Rett syndrome (RTT; MIM312750), a neurodevelopmental disorder predominantly occurring in females, is caused in the majority of cases by sporadic mutations in the gene encoding the transcriptional modulator Methyl-CpG-Binding Protein 2 (MECP2). In mice, impaired MeCP2 function results in severe motor, cognitive, and emotional defects. However, the impact of Mecp2 function on the development and organization of the cortical inhibitory system is still largely unknown. First, we found that MeCP2 expression varies among the major γ-aminobutyric acid-(GABA)-releasing cortical interneurons (INs) subclasses and its nuclear localization differs between neuronal types. The density of calretinin(+) and parvalbumin(+) INs increases in Mecp2 knockout mice (Mecp2(-/y) ) already at early postnatal developmental stages. In contrast, the density of somatostatin(+) INs is not affected. We also found that the development of multipolar-calretinin(+) interneurons is selectively affected by the absence of Mecp2. Additionally, we show that in Mecp2 heterozygous female mice, a model closely mimicking human RTT condition, INs abnormalities are similar to those observed in Mecp2(-/y) mice. Together, our study indicates that loss of function of Mecp2 strongly interferes with the correct establishment of the neocortical inhibitory system producing effects that are specific to different IN subtypes. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 06/2014;
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    ABSTRACT: Read the full article ‘Cdk5/p35 is required for motor coordination and cerebellar plasticity’ on page doi: 53.
    Journal of Neurochemistry 06/2014;
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    ABSTRACT: Human glioblastomas may be hierarchically organized. Within this hierarchy, glioblastoma-initiating cells (GIC) have been proposed to be more resistant to radiochemotherapy and responsible for recurrence. Here, established stem cell markers and stem cell attributed characteristics such as self-renewal capacity and tumorigenicity have been profiled in primary glioblastoma cultures to predict radiosensitivity. Furthermore, the sensitivity to radiotherapy of different subpopulations within a single primary glioblastoma culture was analyzed by a flow cytometric approach using Nestin, SRY (sex determining region Y)-box 2 (SOX2) and glial fibrillary acidic protein (GFAP). The protein expression of Nestin and SOX2 as well as the mRNA levels of Musashi1, L1CAM, CD133, Nestin and PLAGL2 inversely correlated with radioresistance in regard to the clonogenic potential. Only CD44 protein expression correlated positively with radioresistance. In terms of proliferation, Nestin protein expression and Musashi1, PLAGL2 and CD133 mRNA levels inversely correlated with radioresistance. Higher expression of stem cell markers does not correlate with resistance to radiochemotherapy in a TCGA (the cancer genome atlas) glioblastoma collective. SOX2 expressing subpopulations exist within single primary glioblastoma cultures. These subpopulations predominantly form the proliferative pool of the primary cultures and are sensitive to irradiation. Thus, profiling of established stem cell markers revealed a surprising result. Except CD44, the tested stem cell markers showed an inverse correlation between expression and radioresistance. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 06/2014;
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    ABSTRACT: This study investigated effects of IOX3, a selective small molecule inhibitor of hypoxia inducible factor (HIF) prolyl hydroxylases, on mouse brains subject to transient focal cerebral ischaemia. Male, 8-12 week old C57/B6 mice were subjected to 45min of middle cerebral artery occlusion (MCAO) either immediately or 24h after receiving IOX3. Mice receiving IOX3 at 20 mg.kg(-1) 24h prior to the MCAO had better neuroscores and smaller blood brain barrier (BBB) disruption and infarct volumes than mice receiving the vehicle, while those having IOX3 at 60 mg.kg(-1) showed no significant changes. IOX3 treatment immediately before MCAO was not neuroprotective. IOX3 upregulated HIF1α, and increased EPO expression in mouse brains. In an in vitro BBB model (RBE4 cell line), IOX3 upregulated HIF1α and delocalized ZO-1. Pretreating IOX3 on RBE4 cells 24h before oxygen glucose deprivation (OGD) had a protective effect on endothelial barrier preservation with ZO-1 being better localized, while immediate IOX3 treatment did not. Our study suggests that HIF stabilization with IOX3 before cerebral ischaemia is neuroprotective partially due to BBB protection, while immediate application could be detrimental. These results provide information for studies aimed at the therapeutic activation of HIF pathway for neurovascular protection from cerebral ischaemia. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 06/2014;
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    ABSTRACT: Genetic studies show that LRRK2, and not its closest paralogue LRRK1, is linked to Parkinson's disease. To gain insight into the molecular and cellular basis of this discrepancy, we searched for LRRK1- and LRRK2-specific cellular processes by identifying their distinct interacting proteins. A protein microarray-based interaction screen was performed with recombinant 3xFlag-LRRK1 and 3xFlag-LRRK2 and, in parallel, co-immunoprecipitation followed by mass spectrometry was performed from SH-SY5Y neuroblastoma cell lines stably expressing 3xFlag-LRRK1 or 3xFlag-LRRK2. We identified a set of LRRK1- and LRRK2-specific as well as common interactors. One of our most prominent findings was that both screens pointed to epidermal growth factor receptor (EGF-R) as a LRRK1-specific interactor, while 14-3-3 proteins were LRRK2-specific. This is consistent with phosphosite mapping of LRRK1, revealing phosphosites outside of 14-3-3 consensus binding motifs. To assess the functional relevance of these interactions, SH-SY5Y-LRRK1 and -LRRK2 cell lines were treated with LRRK2 kinase inhibitors that disrupt 14-3-3 binding, or with EGF, an EGF-R agonist. Redistribution of LRRK2, not LRRK1, from diffuse cytoplasmic to filamentous aggregates was observed after inhibitor treatment. Similarly, EGF induced translocation of LRRK1, but not of LRRK2, to endosomes. Our study confirms that LRRK1 and LRRK2 can carry out distinct functions by interacting with different cellular proteins. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 06/2014;
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    ABSTRACT: Hypoxia-inducible factor (HIF)-1 is the key transcriptional activator mediating both adaptive and pathological responses to hypoxia. The purpose of this study was to find the role of HIF-1 in regulating neprilysin (NEP) at the early stage of hypoxia and explore the underlying mechanism. In the present study, we demonstrate that both NEP mRNA and protein levels in neuroblastoma cells were elevated in early stages of hypoxia. Over-expression of HIF-1α gene increased NEP mRNA/protein levels, as well as enzyme activity while knockdown of HIF-1α decreased them. Meanwhile, HIF-1α was shown to bind to histone deacetylase (HDAC)-1 and reduced the association of HDAC-1 with NEP promoter, thus activating NEP gene transcription in a de-repression way. In summary, our results indicated that hypoxia in the early stages would up-regulate NEP expression, in which interaction of HIF-1α and HDAC-1 may play a role. This study suggested that NEP up-regulation might be an adaptive response to hypoxia, which was mediated by HIF-1α binding to HDAC-1 at the early stage of hypoxia. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 06/2014;