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

Abstract:

: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.

journal_name

J Neurochem

authors

Jin K,Mao XO,Zhu Y,Greenberg DA

doi

10.1046/j.0022-3042.2001.00678.x

keywords:

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

119-25

issue

1

eissn

0022-3042

issn

1471-4159

journal_volume

80

pub_type

杂志文章
  • Variables influencing the effect of a meal on brain tryptophan.

    abstract::Previous work from our laboratory points to plasma free tryptophan being a useful predictor of brain tryptophan concentration in many circumstances. Other work, in particular various studies on the acute effects of food intake, has emphasized the roles of plasma total tryptophan and of plasma large neutral amino acids...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1985.tb08797.x

    authors: Sarna GS,Kantamaneni BD,Curzon G

    更新日期:1985-05-01 00:00:00

  • [3H]spiroxatrine: a 5-HT1A radioligand with agonist binding properties.

    abstract::Spiroxatrine has been reported to be a 5-HT1A serotonin receptor antagonist. Therefore [3H]spiroxatrine was synthesized and its 5-HT1A receptor binding properties in homogenates of rat hippocampal membranes were characterized with the expectation that it would be the first 5-HT1A antagonist radioligand. [3H]8-Hydroxyd...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1988.tb02943.x

    authors: Herrick-Davis K,Titeler M

    更新日期:1988-02-01 00:00:00

  • Enhancement of apoptosis in developing chick neural retina cells by basic fibroblast growth factor.

    abstract::To evaluate the role of various growth factors in naturally occurring cell death during development of the neural retina, we examined the effects of such factors on the nuclear morphology and the size of DNA in cultured chick embryonic neural retina cells. Basic fibroblast growth factor (bFGF) increased internucleosom...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1997.68052212.x

    authors: Yokoyama Y,Ozawa S,Seyama Y,Namiki H,Hayashi Y,Kaji K,Shirama K,Shioda M,Kano K

    更新日期:1997-05-01 00:00:00

  • Resistance to disruption of multilamellar fragments of central nervous system myelin.

    abstract::Single-bilayer vesicles of myelin are desirable for studying myelin development and metabolism. Accordingly, our interest was drawn to a procedure for vesiculating myelin (Steck et al., Biochim, Biophys. Acta 509, 397-408, 1978). We used X-ray diffraction analysis to examine these putative vesicle preparations because...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1984.tb05402.x

    authors: Sedzik J,Toews AD,Blaurock AE,Morell P

    更新日期:1984-11-01 00:00:00

  • Characterization of the thyroid hormone transport system of cerebrocortical rat neurons in primary culture.

    abstract::The uptake of 3',3,5-triiodo-L-thyronine (T3) and L-thyroxine (T4) by primary cultures derived from rat brain hemispheres was studied under initial velocity conditions, at 25 degrees C. Uptake of both hormones was carrier mediated and obeyed simple Michaelis-Menten kinetics. The Km of T3 uptake was very similar to tha...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1995.65062549.x

    authors: Chantoux F,Blondeau JP,Francon J

    更新日期:1995-12-01 00:00:00

  • Evidence that 5'-cytidinediphosphocholine can affect brain phospholipid composition by increasing choline and cytidine plasma levels.

    abstract::We examined the effects of orally administered 5'-cytidinediphosphocholine (CDP-choline) on arterial plasma choline and cytidine levels and on brain phospholipid composition in rats. Animals receiving a single oral dose of 100, 250, or 500 mg/kg showed peak plasma choline levels 6-8 h after drug administration (from 1...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1995.65020889.x

    authors: López-Coviella I,Agut J,Savci V,Ortiz JA,Wurtman RJ

    更新日期:1995-08-01 00:00:00

  • SNARE proteins--why so many, why so few?

    abstract::Both trafficking and secretion critically depend on accurate and specific membrane recognition and fusion. A key step in these processes is the assembly of a complex consisting of a small number of proteins, i.e., the exocytic core complex. In nerve terminals, this set consists of VAMP and synaptotagmin, which reside ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审

    doi:10.1046/j.1471-4159.1997.69051781.x

    authors: Linial M

    更新日期:1997-11-01 00:00:00

  • Potassium-induced stimulation of glutamate uptake in mouse cerebral astrocytes: the role of intracellular pH.

    abstract::The Na(+)-glutamate cotransporters are believed to countertransport OH- and K+. Previous evidence that the velocity of glutamate uptake can exceed the acid extrusion capacity of astrocytes raised the question of whether intracellular pH can become rate limiting for glutamate uptake. Cytoplasmic buffering capacity and ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1996.66010169.x

    authors: Judd MG,Nagaraja TN,Brookes N

    更新日期:1996-01-01 00:00:00

  • Role of histidine residues in the adenosine A2a receptor ligand binding site.

    abstract::The pH dependency of the binding of ligands to adenosine A2a receptors in rat striatal membranes was examined. For those agonists sensitive to adenosine deaminase a solubilised membrane preparation was used. A two- to fourfold increase in affinity was observed for CGS-21680, 5'-N-ethylcarboxamidoadenosine, adenosine, ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1994.63041477.x

    authors: Askalan R,Richardson PJ

    更新日期:1994-10-01 00:00:00

  • Intermediate filament disassembly in cultured dorsal root ganglion neurons is associated with amino-terminal head domain phosphorylation of specific subunits.

    abstract::We previously reported that activation of protein kinase A in cultured rat dorsal root ganglion neurons, treated concomitantly with low concentrations of okadaic acid that selectively inhibit protein phosphatase-2A, enhanced the Triton X-100 solubility of neurofilament triplet proteins. We now show that peripherin and...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1998.70051869.x

    authors: Giasson BI,Mushynski WE

    更新日期:1998-05-01 00:00:00

  • Phosphoinositide 3-kinase mediated signaling in lobster olfactory receptor neurons.

    abstract::In vertebrates and some invertebrates, odorant molecules bind to G protein-coupled receptors on olfactory receptor neurons (ORNs) to initiate signal transduction. Phosphoinositide 3-kinase (PI3K) activity has been implicated physiologically in olfactory signal transduction, suggesting a potential role for a G protein-...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2010.06597.x

    authors: Corey EA,Bobkov Y,Pezier A,Ache BW

    更新日期:2010-04-01 00:00:00

  • Genetic deletion of monoacylglycerol lipase leads to impaired cannabinoid receptor CB₁R signaling and anxiety-like behavior.

    abstract::Endocannabinoids (eCB) are key regulators of excitatory/inhibitory neurotransmission at cannabinoid-1-receptor (CB1 R)-expressing axon terminals. The most abundant eCB in the brain, that is 2-arachidonoylglycerol (2-AG), is hydrolyzed by the enzyme monoacylglycerol lipase (MAGL), whose chronic inhibition in the brain ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.13267

    authors: Imperatore R,Morello G,Luongo L,Taschler U,Romano R,De Gregorio D,Belardo C,Maione S,Di Marzo V,Cristino L

    更新日期:2015-11-01 00:00:00

  • A novel anticonvulsant modulates voltage-gated sodium channel inactivation and prevents kindling-induced seizures.

    abstract::Here, we explore the mechanism of action of isoxylitone (ISOX), a molecule discovered in the plant Delphinium denudatum, which has been shown to have anticonvulsant properties. Patch-clamp electrophysiology assayed the activity of ISOX on voltage-gated sodium channels (VGSCs) in both cultured neurons and brain slices ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.12352

    authors: Ashraf MN,Gavrilovici C,Shah SU,Shaheen F,Choudhary MI,Rahman AU,Fahnestock M,Simjee SU,Poulter MO

    更新日期:2013-09-01 00:00:00

  • Ascorbate-stimulated lipid peroxidation in human brain is dependent on iron but not on hydroxyl radical.

    abstract::Lipid peroxidation has been postulated as a cause of neuronal damage in both aging and neurodegenerative disease. In studies of neurodegenerative disease, iron, iron plus ascorbate, or ascorbate alone has been used to stimulate lipid peroxidation. The mechanism by which ascorbate stimulates lipid peroxidation in human...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1996.67020717.x

    authors: Andorn AC,Britton RS,Bacon BR

    更新日期:1996-08-01 00:00:00

  • Tanycytes: Gateway to the hungry brain: An Editorial for "The FGF2-induced tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway" on https://doi.org/10.1111/jnc.15188.

    abstract::Tanycytes are glial cells in the hypothalamus that are functionally part of the blood-brain barrier. They can sense nutrients and metabolites in the circulation such as glucose, then signal to neuronal systems to influence ingestive behaviour and energy storage, and ultimately affect body weight. The complex structure...

    journal_title:Journal of neurochemistry

    pub_type: 社论

    doi:10.1111/jnc.15218

    authors: Ebling FJP

    更新日期:2020-11-09 00:00:00

  • Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71.

    abstract::Alzheimer's disease (AD) is a neurodegenerative disorder in which oxidative stress has been implicated as an important event in the progression of the pathology. In particular, it has been shown that protein modification by reactive oxygen species (ROS) occurs to a greater extent in AD than in control brain, suggestin...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2002.01103.x

    authors: Castegna A,Aksenov M,Thongboonkerd V,Klein JB,Pierce WM,Booze R,Markesbery WR,Butterfield DA

    更新日期:2002-09-01 00:00:00

  • Interspecies comparison of brain ganglioside patterns studied by two-dimensional thin-layer chromatography.

    abstract::Brain gangliosides from four vertebrate classes (fish, amphibia, aves, and mammalia) were studied by patterns generated with the use of two-dimensional thin-layer chromatography. In an effort to retain possible alkalilabile gangliosides, samples were not base-hydrolyzed. Resultant chromatograms revealed complex patter...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1981.tb04490.x

    authors: Hunter GD,Wiegant VM,Dunn AJ

    更新日期:1981-10-01 00:00:00

  • Adult neurogenesis and its role in brain injury and psychiatric diseases.

    abstract::In the adult mammalian brain, neural stem cells (NSCs) reside in two neurogenic regions, the walls of the lateral ventricles, and the subgranular zone of the hippocampus, which generate new neurons for the olfactory bulb and dentate gyrus, respectively. These adult NSCs retain their self-renewal ability and capacity t...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审

    doi:10.1111/jnc.14557

    authors: Hayashi Y,Jinnou H,Sawamoto K,Hitoshi S

    更新日期:2018-12-01 00:00:00

  • Choline acetyltransferase activity and total protein content in selected optic areas of the rat after complete light-deprivation during CNS development.

    abstract::Choline acetyltransferase (acetyl-CoA: choline O-acetyltransferase, I.U.B. 2.3.1.6) activity and total protein content in visual and extra-visual areas were compared in normal Long-Evans rats and in rats subjected to complete light-deprivation for 21 days from birth. The enzyme activity and the protein content in the ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1968.tb10323.x

    authors: Maletta GJ,Timiras PS

    更新日期:1968-08-01 00:00:00

  • Insulin-like growth factor binding protein-1 activates integrin-mediated intracellular signaling and migration in oligodendrocytes.

    abstract::In multiple sclerosis (MS), oligodendrocytes in lesions are lost, leaving damaged tissue virtually devoid of these myelin-producing cells. Our group has recently demonstrated enhanced expression of insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) in oligodendrocytes (CNPase(+)) localized adjacent to MS les...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2010.06703.x

    authors: Chesik D,De Keyser J,Bron R,Fuhler GM

    更新日期:2010-06-01 00:00:00

  • Modulation of cerebral vascular tone by activated glia: involvement of nitric oxide.

    abstract::The ability of activated glia to affect cerebral vascular tone has been evaluated using an in vitro experimental system in which basilar arteries were incubated with glial cultures activated by treatment with lipopolysaccharide (LPS). Vascular tone was measured with an isometric myograph. Contraction in response to hi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2004.02782.x

    authors: Chisari M,Salomone S,Laureanti F,Copani A,Sortino MA

    更新日期:2004-12-01 00:00:00

  • Microtubule dynamics and the neurodegenerative triad of Alzheimer's disease: The hidden connection.

    abstract::Alzheimer's disease (AD) is the most common neurodegenerative disorder and is, on a histopathological level, characterized by the presence of extracellular amyloid plaques composed of the protein fragment Aβ, and intracellular neurofibrillary tangles, which contain the microtubule-associated protein tau in a hyperphos...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审

    doi:10.1111/jnc.14011

    authors: Brandt R,Bakota L

    更新日期:2017-11-01 00:00:00

  • Ontogeny of calcium antagonist binding sites in chick brain and heart.

    abstract::The ontogeny of chick brain and heart ventricle calcium antagonist binding sites was determined, using [3H]nitrendipine ([3H]NDP), as the ligand. The binding of [3H]NDP to adult heart and brain was kinetically very similar, with the former displaying a KD of 0.28 +/- 0.02 nM and a Bmax of 138 +/- 17 fmol/mg protein, a...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1984.tb02792.x

    authors: Marangos PJ,Sperelakis N,Patel J

    更新日期:1984-05-01 00:00:00

  • Enhancement by cytidine of membrane phospholipid synthesis.

    abstract::Cytidine, as cytidine 5'-diphosphate choline, is a major precursor in the synthesis of phosphatidylcholine in cell membranes. In the present study, we examined the relationships between extracellular levels of cytidine, the conversion of [14C]choline to [14C]phosphatidylcholine, and the net syntheses of phosphatidylch...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1992.tb08909.x

    authors: G-Coviella IL,Wurtman RJ

    更新日期:1992-07-01 00:00:00

  • The position of an arginine residue influences substrate affinity and K+ coupling in the human glutamate transporter, EAAT1.

    abstract::Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system and extracellular glutamate levels are controlled by a family of transporters known as excitatory amino acid transporters (EAATs). The EAATs transport glutamate and aspartate with similar micromolar affinities and this tra...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2010.06796.x

    authors: Ryan RM,Kortt NC,Sirivanta T,Vandenberg RJ

    更新日期:2010-07-01 00:00:00

  • A comparison of axonal and somatodendritic dopamine release using in vivo dialysis.

    abstract::The release of endogenous dopamine from the axon terminal field in the nucleus accumbens and from the A10 dopamine cell bodies of conscious rats was measured using intracranial dialysis. Release of dopamine from both areas was calcium-dependent and markedly inhibited by the presence of the D2 agonist, quinpirole, in t...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1991.tb02015.x

    authors: Kalivas PW,Duffy P

    更新日期:1991-03-01 00:00:00

  • Release of previously incorporated gamma-[3H]aminobutyric acid in rabbit caudate nucleus slices.

    abstract::The release of gamma-aminobutyric acid (GABA) was studied in slices of the head of the rabbit caudate nucleus. The slices were preincubated with [3H]GABA and then superfused. Aminooxyacetic acid was present throughout. Both the tritium in the slices and that in the superfusate consisted practically entirely of [3H]GAB...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1986.tb00624.x

    authors: Limberger N,Späth L,Starke K

    更新日期:1986-04-01 00:00:00

  • The effect of some precursor amino acids and enzyme inhibitors on the mouse striatal concentration of tyramines and homovanillic acid.

    abstract::The parenteral administration of L-phenylalanine or p-tyrosine increases the mouse striatal concentration of p-tyramine, an effect that is enhanced by monoamine oxidase inhibition and reduced by an L-aromatic aminoacid decarboxylase inhibitor. Striatal m-tyramine was increased following administration of L-phenylalani...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1982.tb07971.x

    authors: Juorio AV,Boulton AA

    更新日期:1982-09-01 00:00:00

  • Evidence for a single protein kinase C-mediated phosphorylation site in rat brain protein B-50.

    abstract::The neuronal protein B-50 may be involved in diverse functions including neural development, axonal regeneration, neural plasticity, and synaptic transmission. The rat B-50 sequence contains 226 amino acids which include 14 Ser and 14 Thr residues, all putative sites for phosphorylation by calcium/phospholipid-depende...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1989.tb09259.x

    authors: Coggins PJ,Zwiers H

    更新日期:1989-12-01 00:00:00

  • Synaptic concentration of dopamine in the mouse striatum in relationship to the kinetic properties of the dopamine receptors and uptake mechanism.

    abstract::The concentration of dopamine (DA) in the synaptic cleft in the mouse striatum in vivo was estimated from the competition between the synaptic DA and the 3H-labelled DA D2 receptor agonists N-n-propylnorapomorphine (NPA) or N,N-diethyl-N'-[(3 alpha, 4a alpha, 10 beta)-1,2,3,4,4a,5,10,10a-octahydro- 7-hydroxyl-1-propyl...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1991.tb02557.x

    authors: Ross SB

    更新日期:1991-01-01 00:00:00