Abstract:
:Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, D-glucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an in vitro model of ischemic stroke. Collectively, such evidence suggests that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented. Mammalian hibernation provides a valuable model of tolerance to ischemic stress. Herein, we demonstrate that marked reductions in the phosphorylation of ribosomal protein S6 (rpS6), extracellular signal-regulated kinase family of mitogen-activated protein (MAP) kinase p44/42 (p44/42MAPK) and ribosomal protein S6 kinase (S6K) occur within the brains of both hibernating squirrels and rats, which have undergone an ischemic preconditioning paradigm. We therefore propose that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning, via a suppression of protein synthesis and/or energy consumption.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Miyake S,Wakita H,Bernstock JD,Castri P,Ruetzler C,Miyake J,Lee YJ,Hallenbeck JMdoi
10.1111/jnc.13368subject
Has Abstractpub_date
2015-12-01 00:00:00pages
943-57issue
5eissn
0022-3042issn
1471-4159journal_volume
135pub_type
杂志文章abstract::Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce A beta production by functionally inhibiting gamma-secretase, the activity responsible for the carboxy-terminal cleavage required for A beta production. These mo...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00012.x
更新日期:2001-01-01 00:00:00
abstract::Neurofibrillary tangles, one of the major pathological hallmarks of Alzheimer-diseased brains, consist primarily of aggregated paired helical filaments (PHFs) of hyperphosphorylated tau protein. Tau from normal brain and especially from foetal brain is also phosphorylated on some of the sites phosphorylated in PHFs, m...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69010191.x
更新日期:1997-07-01 00:00:00
abstract::The hydrolysis of phosphoinositides (PI) elicited in cerebellar granule cell cultures by agonists of metabolotropic glutamate receptors, glutmate and quisqualate, was enhanced when the cells were pretreated with concanavalin A (Con-A). A similar effect was produced by wheat germ agglutinin, but not by several other le...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb03474.x
更新日期:1991-06-01 00:00:00
abstract::Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR). The molecular events promoting BDNF-mediated pro-death signalling in hyp...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14609
更新日期:2019-01-01 00:00:00
abstract::Neuroleptics are thought to exert their anti-psychotic effects by counteracting a hyper-dopaminergic transmission. Here, we have examined the dopaminergic status of STOP (stable tubule only polypeptide) null mice, which lack a microtubule-stabilizing protein and which display neuroleptic-sensitive behavioural disorder...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03166.x
更新日期:2005-07-01 00:00:00
abstract::Measurements were made of the amino acid content of a cellular clone (K55) derived from mouse cerebellar cultures transformed in vitro by simian virus-40 (Alliot and Pessac, 1981) and that appears to be astroglial. Both the total amount of amino acids as well as the percentage of glycine in K55 cells were higher than ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1983.tb13564.x
更新日期:1983-05-01 00:00:00
abstract::Drosophila melanogaster homogenates incubated with tritiated 5-hydroxytryptophan, 5-hydroxytryptamine, or N-acetylserotonin have the ability of converting them into labelled indolamines, including melatonin. All these compounds were characterized by two-dimensional thin-layer chromatography by comparison with nonradio...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb02923.x
更新日期:1988-02-01 00:00:00
abstract::Neurocatin, a neuroregulatory factor isolated from mammalian brain, is a powerful affector of protein phosphorylation in rat striatal synaptosomes. Two major synaptosomal phosphoproteins of approximately 80 and approximately 60 kDa, possibly synapsin I and tyrosine hydroxylase, were especially sensitive to neurocatin....
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb03280.x
更新日期:1993-04-01 00:00:00
abstract::In contrast to typical neuroleptic drugs, which have high affinities for dopamine D2 receptors, clozapine binds to multiple neurotransmitter receptors. The mechanisms responsible for its superior clinical efficacy over typical neuroleptics remain unknown. Using an automated genomics approach, total gene expression ana...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00027.x
更新日期:2001-02-01 00:00:00
abstract::Arachidonic acid (AA) plays an important role as a signaling factor in the CNS. Therefore, exposure to AA may affect cholinergic neurons in the spinal cord. To test this hypothesis, mRNA expression and activity of choline acetyltransferase (ChAT) was measured in cultured spinal cord neurons treated with increasing con...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02535.x
更新日期:2004-08-01 00:00:00
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 this study, we demonstrated ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12795
更新日期:2014-10-01 00:00:00
abstract::The neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) in the brain striatum has recently been shown to bind at a putatively vesicular site labeled by [3H]tyramine ([3H]TY). Whereas in the rat and mouse striatum MPP+ antagonized TY binding competitively, in the cerebellum there was a mixed-type antagonism, which sugges...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb03212.x
更新日期:1993-02-01 00:00:00
abstract::The Kölliker-Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in respiration and upper airway control. A comprehensive understanding of the KF and its contributions to respiratory function and dysfunction requires a...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/jnc.15041
更新日期:2021-01-01 00:00:00
abstract::We have previously shown that in cell extracts from rat striatum, cyclic AMP response element (CRE) binding protein (CREB), rather than AP-1 proteins, preferentially interacts with the CRE-2 element of the proenkephalin second messenger-inducible enhancer, even under conditions in which AP-1 proteins are highly induce...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.65031007.x
更新日期:1995-09-01 00:00:00
abstract::The structure and function of mitochondrial respiratory-chain enzyme proteins were studied postmortem in the substantia nigra of nine patients with Parkinson's disease and nine matched controls. Total protein and mitochondrial mass were similar in the two groups. NADH-ubiquinone reductase (Complex I) and NADH cytochro...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb02325.x
更新日期:1990-03-01 00:00:00
abstract::Iron, an essential element for all cells of the body, including those of the brain, is transported bound to transferrin in the blood and the general extracellular fluid of the body. The demonstration of transferrin receptors on brain capillary endothelial cells (BCECs) more than 20 years ago provided the evidence for ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2007.04976.x
更新日期:2007-12-01 00:00:00
abstract::A decline in the calcium-dependent release of neurotransmitters appears to underlie the decreased neuronal function that accompanies reduced oxygen tensions (hypoxia). To determine if alterations in calcium uptake are primary to these changes, synaptosomal calcium uptake was measured in the presence of 100%, 2.5%, or ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb09725.x
更新日期:1984-01-01 00:00:00
abstract::Interleukin-1β (IL-1β) is released from activated microglia and involved in the neurodegeneration of acute and chronic brain disorders, such as stroke and Alzheimer's disease, in which extracellular acidification has been shown to occur. Here, we examined the extracellular acidic pH regulation of IL-1β production, esp...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12661
更新日期:2014-05-01 00:00:00
abstract::Dermorphin and its Hyp6 analogue are opiate-like heptapeptides originally discovered in frog skin and characterized by the presence of a D-Ala2 residue in their sequence. They were assayed for their capacity to compete with [3H]Leu-enkephalin for binding to opioid receptors in membranes of neuroblastoma x glioma hybri...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb06336.x
更新日期:1981-12-01 00:00:00
abstract::In PC12 cells, preincubated with [3H]inositol, nerve growth factor (NGF) stimulated an approximately 100% increase in the levels of [3H]inositol 1,3,4-trisphosphate ([3H]-Ins(1,3,4)P3], [3H]inositol 1,4,5-trisphosphate ([3H]Ins(1,4,5)P3], and [3H]inositol 1,3,4,5-tetrakisphosphate ([3H]Ins(1,3,4,5)P4] as early as 5-15...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb03617.x
更新日期:1993-09-01 00:00:00
abstract::5-HT(3) (serotonin type 3) receptors are targets of antiemetics, antipsychotics, and antidepressants and are believed to play a role in cognition. Nevertheless, contrasting results have been obtained with respect to their functions in the CNS and in the control of transmitter release. We used rat hippocampal neurons i...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.04218.x
更新日期:2007-01-01 00:00:00
abstract::L-3,4-Dihydroxyphenylalanine (L-dopa) is toxic for human neuroblastoma cells NB69 and its toxicity is related to several mechanisms including quinone formation and enhanced production of free radicals related to the metabolism of dopamine via monoamine oxidase type B. We studied the effect of L-DOPA on activities of e...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.64020576.x
更新日期:1995-02-01 00:00:00
abstract::Although the excitatory action of GABA has been shown to activate the expression of brain-derived neurotrophic factor (BDNF), its molecular mechanisms remain unclear. Using cultured rat cortical cells, we here demonstrated that GABA induced Bdnf mRNA expression mainly via L-type voltage-dependent Ca(2+) channels (L-VD...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12801
更新日期:2014-10-01 00:00:00
abstract::The regional and developmental expression of NMDA receptors containing the NR2D subunit was analyzed on the level of the subunit mRNA and protein in rat brain. RNase protection experiments indicated that among two proposed splice variants of the NR2D subunit, only the NR2D-2 subunit is expressed. The regional distribu...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.66031240.x
更新日期:1996-03-01 00:00:00
abstract::Docosahexaenoic acid (DHA), an n-3 fatty acid, is rapidly deposited during the period of rapid brain development. The influence of n-3 fatty acid deficiency on learning performance in adult rats over two generations was investigated. Rats were fed either an n-3 fatty acid-adequate (n-3 Adq) or -deficient (n-3 Def) die...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0752563.x
更新日期:2000-12-01 00:00:00
abstract::Excitotoxicity, caused by exaggerated neuronal stimulation by Glutamate (Glu), is a major cause of neurodegeneration in brain ischemia. While we know that neurodegeneration is triggered by overstimulation of Glu-receptors (GluRs), the subsequent mechanisms that lead to cellular demise remain controversial. Surprisingl...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14629
更新日期:2019-02-01 00:00:00
abstract::Neuronal nicotinic acetylcholine receptors labelled with tritiated agonists are reduced in the cerebral cortex in Alzheimer's disease (AD), but to date it has not been demonstrated which nicotinic receptor subunits contribute to this deficit. In the present study, autopsy tissue from the temporal cortex of 14 AD cases...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0731635.x
更新日期:1999-10-01 00:00:00
abstract::Edaravone (Eda) is a potent scavenger of hydroxyl radicals and has been demonstrated to be beneficial for patients with acute ischemic stroke. This study was set out to investigate whether Eda protect against MPP(+)-induced cytotoxicity in rat primary cultured astrocytes. The results showed that pre-treatment with Eda...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05573.x
更新日期:2008-09-01 00:00:00
abstract::Carbamylcholine stimulated phospholipase C activity in astrocytes in primary culture from the mesencephalon but not from the striatum or cerebral cortex of the mouse embryo. An alpha 1-adrenergic-mediated response was observed in all astrocyte populations. 2-Chloroadenosine potentiated the alpha 1-adrenergic response ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb02551.x
更新日期:1989-03-01 00:00:00
abstract::In the presence of lithium, carbamylcholine chloride (carbachol) and epinephrine increase the accumulation of inositol monophosphate severalfold in hippocampal slices from the rat. The stimulation by carbachol (EC50, 31 microM) is mediated by muscarinic receptors, whereas the effects of epinephrine (EC50, 2 microM) ar...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb02947.x
更新日期:1988-02-01 00:00:00