MEK and ERK protect hypoxic cortical neurons via phosphorylation of Bad.


:We investigated the role of mitogen-activated protein kinase (MAPK) pathways in hypoxic neuronal injury using primary cultures from murine cerebral cortex. Hypoxia caused the death of approximately 50% of neurons at 16 h and approximately 65% of neurons at 24 h. This was associated with phospho-activation of the MAPK/extracellular signal-regulated kinase (ERK) kinase MEK1/2 and its downstream target ERK1/2, but not p38 MAPK or c-Jun N-terminal kinase (JNK), as detected by western blotting. The MEK1/2 inhibitor, PD98059, increased neuronal death in hypoxic cultures, suggesting that MEK1/2 promotes neuronal survival, whereas the p38 inhibitors, SB202190 and SB203580, had no effect. To identify downstream effects of ERK1/2 that might regulate hypoxic neuronal death, we measured hypoxia-induced phosphorylation of three ERK1/2 targets: the 90-kDa ribosomal protein S6 kinase (RSK), the transcription factor ELK1, and the pro-apoptotic Bcl-2 family protein Bad. We observed increased abundance of inactivated (phospho-)Bad, but no change in phospho-RSK or phospho-ELK1. Moreover, the MEK inhibitor PD98059 reduced phospho-inactivation of Bad in hypoxic cultures. These findings suggest that a cell-survival program involving phospho-activation of MEK1/2 and ERK1/2 and inactivation of Bad is mobilized in hypoxic neurons, and may help to regulate neuronal fate following hypoxic-ischemic injury.


J Neurochem


Jin K,Mao XO,Zhu Y,Greenberg DA





Has Abstract


2002-01-01 00:00:00












  • Fast-transported glycoproteins and nonglycosylated proteins contain sulfate.

    abstract::35SO4-labeled fast-transported proteins of bullfrog dorsal root ganglion neurons were separated by two-dimensional gel electrophoresis, and their mobilities were compared to similar species labeled with [3H]mannose or [3H]fucose. Fluorography revealed regions of poorly resolved, high molecular weight material, likely ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Stone GC,Hammerschlag R,Bobinski JA

    更新日期:1983-10-01 00:00:00

  • Low-density lipoprotein receptor-related protein levels and endocytic function are reduced by overexpression of the FE65 adaptor protein, FE65L1.

    abstract::The FE65 adaptor protein family was identified in two-hybrid screens as proteins that bind the cytoplasmic domain of the amyloid precursor protein (APP). Studies have shown that FE65 binding to APP modulates APP processing. Increased levels of alpha-secretase derived secreted APP (APPsalpha) and beta-amyloid (Abeta) w...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Guénette SY,Chang Y,Hyman BT,Tanzi RE,Rebeck GW

    更新日期:2002-08-01 00:00:00

  • Human Y-79 retinoblastoma cells exhibit specific insulin receptors.

    abstract::The presence of insulin receptors was investigated in human Y-79 retinoblastoma cells grown in suspension culture. The binding of [125I] insulin to these cells was time, temperature, and pH dependent, was competed for by insulin and proinsulin but not other peptides, and was inhibited by antibodies against the insulin...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Saviolakis GA,Kyritsis AP,Chader GJ

    更新日期:1986-07-01 00:00:00

  • Steroidogenic acute regulatory protein (StAR) transcripts constitutively expressed in the adult rat central nervous system: colocalization of StAR, cytochrome P-450SCC (CYP XIA1), and 3beta-hydroxysteroid dehydrogenase in the rat brain.

    abstract::Steroidogenic acute regulatory protein (StAR) is a 30-kDa protein involved in the transport of cholesterol to the inner mitochondrial membrane and thus plays a key role in steroid biosynthesis. To clarify the implications of this protein in neurosteroid biosynthesis, we examined the possible expression of a StAR trans...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Furukawa A,Miyatake A,Ohnishi T,Ichikawa Y

    更新日期:1998-12-01 00:00:00

  • Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons.

    abstract::Increase in oxidative stress has been postulated to play an important role in the pathogenesis of a number of neurodegenerative diseases including Alzheimer's disease. There is evidence for involvement of amyloid-beta peptide (Abeta) in mediating the oxidative damage to neurons. Despite yet unknown mechanism, Abeta ap...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Shelat PB,Chalimoniuk M,Wang JH,Strosznajder JB,Lee JC,Sun AY,Simonyi A,Sun GY

    更新日期:2008-07-01 00:00:00

  • n-3 fatty acid deficiency increases brain protein synthesis in the free-moving adult rat.

    abstract::The autoradiographic method with L-[35S]methionine was used to determine the effects of an n-3 fatty acid deficiency on brain protein synthesis. Brain protein synthesis was significantly increased (from 50 to 150%) in 45 of the 52 brain structures studied in n-3 fatty acid-deficient rats as compared with control anima...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Giaume M,Gay N,Baubet V,Gharib A,Durand G,Bobillier P,Sarda N

    更新日期:1994-11-01 00:00:00

  • Determination of serotonin turnover in the rat brain using 6-fluorotryptophan.

    abstract::After intraperitoneal injection of rats with 6-fluorotryptophan (6-FT), brain 5-hydroxytryptamine (5-HT) levels decreased exponentially over 1 h. Depletion was dose-dependent and maximum depletion was observed at 200 mg/kg. 6-FT (200 mg/kg) did not significantly alter the content of 5-hydroxyindoleacetic acid. Turnove...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Miwa S,Fujiwara M,Lee K,Fujiwara M

    更新日期:1987-05-01 00:00:00

  • ATP inhibits the hypoxia response in type I cells of rat carotid bodies.

    abstract::Summary During hypoxia, ATP was released from type I (glomus) cells in the carotid bodies. We studied the action of ATP on the intracellular Ca(2+) concentration ([Ca(2+)](i)) of type I cells dissociated from rat carotid bodies using a Ca(2+) imaging technique. ATP did not affect the resting [Ca(2+)](i) but strongly s...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Xu J,Xu F,Tse FW,Tse A

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  • Muscular dystrophy in mdx mice despite lack of neuronal nitric oxide synthase.

    abstract::Neuronal nitric oxide synthase (nNOS) is a component of the dystrophin complex in skeletal muscle. The absence of dystrophin protein in Duchenne muscular dystrophy and in mdx mouse causes a redistribution of nNOS from the plasma membrane to the cytosol in muscle cells. Aberrant nNOS activity in the cytosol can induce ...

    journal_title:Journal of neurochemistry

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    authors: Chao DS,Silvagno F,Bredt DS

    更新日期:1998-08-01 00:00:00

  • Nicotine-stimulated release of [3H]norepinephrine from fetal rat locus coeruleus cells in culture.

    abstract::Acute nicotine administration stimulated [3H]norepinephrine ([3H]NE) release from cultured fetal locus coeruleus (LC) cells. The effect was concentration dependent, with an EC50 of 0.9 microM, and was abolished by removal of calcium from, or addition of tetrodotoxin (500 nM) to, the assay buffer. Other nicotinic recep...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Gallardo KA,Leslie FM

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  • Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR-219a-5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1.

    abstract::Circulating microRNAs (miRNAs) have emerged as diagnostic and prognostic biomarkers for traumatic brain injury (TBI). However, a comprehensive characterization of the serum miRNA profile in patients with TBI and the roles of these potential markers in neuronal regulation have rarely been reported. In this study, the l...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Yan J,Bu X,Li Z,Wu J,Wang C,Li D,Song J,Wang J

    更新日期:2019-07-01 00:00:00

  • Nicotinic modulation of [3H]dopamine release from striatal synaptosomes: pharmacological characterisation.

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    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


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  • Quisqualate-stimulated phosphatidylinositol breakdown in rat cerebellar membranes.

    abstract::The effect of quisqualate, an excitatory amino acid agonist, on the breakdown of exogenously added phosphatidylinositol was investigated in a membrane preparation from the cerebellum of young rats. Quisqualate stimulated phospholipase C activity in a dose-dependent manner in the presence of guanosine 5'-O-(3-thiotriph...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


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  • Effects of branched-chain L-amino acids, L-phenylalanine, and L-methionine on the transport of L-glutamine in rat brain cortex in vitro. Influence of cations.

    abstract::Uptake of L-glutamine (2 mM) by rat brain cortex slices against a concentration gradient is markedly inhibited (40%) by branched-chain L-amino acids (1 mM), L-phenylalanine (1 mM), or L-methionine (1 mM); that of L-asparagine (2 mM) is much less affected by these amino acids. Other amino acids investigated have little...

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    pub_type: 杂志文章


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  • Acyl peptide hydrolase, a serine proteinase isolated from conditioned medium of neuroblastoma cells, degrades the amyloid-beta peptide.

    abstract::Considerable evidence indicates that the amyloid-beta (Abeta) peptide, a proteolytic fragment of the amyloid precursor protein, is the pathogenic agent in Alzheimer's disease (AD). A number of proteases have been reported as capable of degrading Abeta, among them: neprilysin, insulin-degrading enzyme, endothelin-conve...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Yamin R,Bagchi S,Hildebrant R,Scaloni A,Widom RL,Abraham CR

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  • Differential effects of hypoxia-ischemia on subunit expression and tyrosine phosphorylation of the NMDA receptor in 7- and 21-day-old rats.

    abstract::The effect of cerebral hypoxia-ischemia (HI) on levels and tyrosine phosphorylation of the NMDA receptor was examined in 7- (P7) and 21 (P21)-day-old rats. Unilateral HI was administered by ligation of the right common carotid artery and exposure to an atmosphere of 8% O2/92% N2 for 2 (P7) or 1.5 (P21) h. This duratio...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Gurd JW,Bissoon N,Beesley PW,Nakazawa T,Yamamoto T,Vannucci SJ

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  • Two-step immunoaffinity purification of acetylcholinesterase from rabbit brain.

    abstract::Acetylcholinesterase (AChE; EC extracted in 1% Triton X-100 from rabbit brain was purified 2,000-fold by chromatography on agarose conjugated with a monoclonal antibody directed against human red blood cell cholinesterase. After elution from the immunoadsorbent with pH 11 buffer, the preparation was purified ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


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  • Leptin neuroprotection in the CNS: mechanisms and therapeutic potentials.

    abstract::Leptin is well known as a hormone important in the central control of appetitive behaviors via receptor-mediated actions in the hypothalamus, where leptin adjusts food intake to maintain homeostasis with the body's energy stores. Recent evidence has shown that leptin and its receptors are widespread in the CNS and may...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审


    authors: Signore AP,Zhang F,Weng Z,Gao Y,Chen J

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  • Novel endogenous 1,2,3,4-tetrahydroisoquinoline derivatives: uptake by dopamine transporter and activity to induce parkinsonism.

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    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Kawai H,Makino Y,Hirobe M,Ohta S

    更新日期:1998-02-01 00:00:00

  • Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer's disease in J20-APP transgenic and wild-type mice.

    abstract::Alzheimer's disease (AD) is a neurodegenerative pathology characterized by aggregates of amyloid-β (Aβ) and phosphorylated tau protein, synaptic dysfunction, and spatial memory impairment. The Wnt signaling pathway has several key functions in the adult brain and has been associated with AD, mainly as a neuroprotectiv...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


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    更新日期:2018-02-01 00:00:00

  • Localization of the RNA-binding proteins Staufen1 and Staufen2 at the mammalian neuromuscular junction.

    abstract::Staufen is an RNA-binding protein, first identified for its role in oogenesis and CNS development in Drosophila. Two mammalian homologs of Staufen have been identified and shown to bind double-stranded RNA and tubulin, and to function in the somatodendritic transport of mRNA in neurons. Here, we examined whether Stauf...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


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  • Effect of intracellular glutamine on the uptake of large neutral amino acids in astrocytes: concentrative Na(+)-independent transport exhibits metastability.

    abstract::To examine whether the concentration gradient of glutamine (Gln) drives concentrative Na(+)-independent uptake of neutral amino acids (NAA) in mouse cerebral astrocytes, uptake was compared in "Gln-depleted" and "Gln-replete" cultures. Uptake (30 min in Na(+)-free buffer) of histidine, kynurenine, leucine, tyrosine, a...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Brookes N

    更新日期:1992-07-01 00:00:00

  • Glutamate inhibition of the adrenergic-stimulated production of melatonin in rat pineal gland in vitro.

    abstract::The effect of L-glutamate on the adrenergic-stimulated release of melatonin in the rat pineal gland was examined using an in vitro perfusion system. L-Glutamate by itself had no effect on melatonin secretion whereas L-glutamate administered prior to (-)-isoproterenol (beta-adrenergic agonist) and L-phenylephrine (alph...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Kus L,Handa RJ,McNulty JA

    更新日期:1994-06-01 00:00:00

  • 1-Piperideine as an in vivo precursor of the gamma-aminobutyric acid homologue 5-aminopentanoic acid.

    abstract::Intraperitoneal injection of the cyclic imine 1-piperideine in mice resulted in measurable quantities of 5-aminopentanoic acid in brain. 5-Aminopentanoic acid is a methylene homologue of gamma-aminobutyric acid (GABA) that is a weak GABA agonist. 5-Aminopentanoic acid formed in the periphery was ruled out as the sourc...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Callery PS,Geelhaar LA

    更新日期:1985-09-01 00:00:00

  • Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology.

    abstract::Parkinson's disease is a progressive neurological disorder that is characterized by the formation of intracellular protein inclusion bodies composed primarily of a misfolded and aggregated form of the protein α-synuclein. There is growing evidence that supports the prion-like hypothesis of α-synuclein progression. Thi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审


    authors: Tyson T,Steiner JA,Brundin P

    更新日期:2016-10-01 00:00:00

  • Increased secretion of adrenomedullin from cultured human astrocytes by cytokines.

    abstract::Adrenomedullin, originally discovered from pheochromocytoma, is a member of the calcitonin gene-related peptide family. The production and secretion of adrenomedullin by cultured human astrocytes were studied by northern blot analysis and radioimmunoassay. Northern blot analysis showed the expression of adrenomedullin...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Takahashi K,Nakayama M,Totsune K,Murakami O,Sone M,Kitamuro T,Yoshinoya A,Shibahara S

    更新日期:2000-01-01 00:00:00

  • Blood-based neurochemical diagnosis of vascular dementia: a pilot study.

    abstract::Blood-based tests for the differential diagnosis of Alzheimer's disease (AD) are under intensive investigation and have shown promising results with regard to Abeta40 and Abeta42 peptide species in incipient AD. Moreover, plasma Abeta40 was suggested as an independent cerebrovascular risk factor candidate. These consi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Bibl M,Esselmann H,Mollenhauer B,Weniger G,Welge V,Liess M,Lewczuk P,Otto M,Schulz JB,Trenkwalder C,Kornhuber J,Wiltfang J

    更新日期:2007-10-01 00:00:00

  • Chromaffin cell death induced by 6-hydroxydopamine is independent of mitochondrial swelling and caspase activation.

    abstract::Our results provide evidence that 6-hydroxydopamine induced, after auto-oxidation, toxic levels of hydrogen peroxide (H2O2) that caused bovine chromaffin cell toxicity and death. 6-Hydroxydopamine (6-OHDA) treatment markedly reduced, in a dose-response fashion, chromaffin cell viability. Cell death was accompanied by ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Galindo MF,Jordán J,González-García C,Ceña V

    更新日期:2003-03-01 00:00:00

  • Multiple functional domains are involved in tomosyn regulation of exocytosis.

    abstract::Tomosyn is a cytoplasmic protein that was shown to bind to Syntaxin1 and SNAP-25 through an R-SNARE domain, forming a complex that is almost identical in structure to the neuronal SNARE complex. Tomosyn inhibits exocytosis in various cell types and these effects were attributed to direct competition between tomosyn's ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Yizhar O,Lipstein N,Gladycheva SE,Matti U,Ernst SA,Rettig J,Stuenkel EL,Ashery U

    更新日期:2007-10-01 00:00:00

  • The membrane cytoskeletal protein adducin is phosphorylated by protein kinase C in D1 neurons of the nucleus accumbens and dorsal striatum following cocaine administration.

    abstract::Repeated cocaine administration results in persistent changes in synaptic function in the mesolimbic dopamine system that are thought to be critical for the transition to addiction. Cytoskeletal rearrangement and actin dynamics are essential for this drug-dependent plasticity. Cocaine administration increases levels o...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章


    authors: Lavaur J,Mineur YS,Picciotto MR

    更新日期:2009-12-01 00:00:00