Abstract:
:We have previously shown that prolonged exposure to neurotrophins induces oxidative neuronal death. In the present study, we further examined the cascades involved in neurotrophin-4/5 (NT-4/5)-induced neuronal death. Exposure of mature cortical cultures for 48 h to NT-4/5 induced neuronal death through TrkB activation. The NT-4/5-induced neuronal death was largely attenuated by addition of MK-801, indicating a critical role for NMDA receptors. Western blots revealed the induction of NR2A by NT-4/5. In addition, levels of phospho-NR2A and 2B increased, suggesting the upregulation of the NMDA receptor function. Whereas glutamate levels in the media changed little, levels of D-serine and L-glycine, co-agonists at NMDA receptors, increased significantly following NT-4/5 treatment. Exposure to NT-4/5 resulted in the activation of Src and extracellular signal-regulated kinase-1/2 (Erk-1/2). Their inhibitors blocked NR2A induction and phosphorylation as well as neuronal death induced by NT-4/5. In addition, Egr-1 was induced in an Src- and Erk-1/2-dependent manner. Anti-sense oligodeoxynucleotides to egr-1 attenuated NR2A induction as well as neuronal death. Although induction of NADPH oxidase and neuronal nitric oxide synthase (nNOS) contributes to NT-4/5-induced neuronal death, inhibition of their activity did not reduce NR2A induction. Conversely, blockade of NMDA receptors did not attenuate induction of NADPH oxidase or nNOS. These results indicate that two events are largely independent of each other. Our results demonstrate that the signaling cascade of TrkB leads to increase in NMDA receptor activity. Whereas this cascade may play an important role in the modulation of NMDA receptors in physiologic conditions, in the context of TrkB overactivation, it may contribute to neuronal death.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Choi SY,Hwang JJ,Koh JYdoi
10.1046/j.1471-4159.2003.02187.xkeywords:
subject
Has Abstractpub_date
2004-02-01 00:00:00pages
708-16issue
3eissn
0022-3042issn
1471-4159pii
2187journal_volume
88pub_type
杂志文章abstract::Stroke is the third leading cause of death as dementia is a main symptom of Alzheimer's disease. One of the important mechanisms in the pathogeny of stroke is free radical production during the reperfusion period, therefore the effects of a type of natural antioxidant, i.e. Crataegus flavonoids (CF), on brain ischemic...
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doi:10.1046/j.1471-4159.1998.71010402.x
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pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb07074.x
更新日期:1980-10-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1983.tb04820.x
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journal_title:Journal of neurochemistry
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pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1990-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb05658.x
更新日期:1987-04-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0732321.x
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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abstract::Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substu...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,多中心研究
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更新日期:2012-04-01 00:00:00
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pub_type: 杂志文章
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abstract::In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata. These plants contain a class of powerful, lipophilic complex I inhibitors, the annonaceous acetogenins. To determine the neurotoxic potential of these sub...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2004-01-01 00:00:00
abstract::We have examined the catecholamine-sensitive adenylate cyclase in the retina of the white perch (Roccus americanus). Both dopamine and the beta-adrenergic agonist isoproterenol stimulate cyclic AMP accumulation in this retina, but serotonin, an indoleamine, and phenylephrine, an alpha-adrenergic agonist, had no effect...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2002-05-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00412.x
更新日期:2001-07-01 00:00:00
abstract::To examine the effects of glutamatergic neurotransmission on amyloid processing, we stably expressed the metabotropic glutamate receptor subtype 1alpha (mGlu-R1alpha) in HEK 293 cells. Both glutamate and the selective metabotropic agonist 1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) rapidly increased phosphatidyli...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1997-08-01 00:00:00
abstract::In the present study, neuronal and Schwann cell marker proteins were used to biochemically characterize the spatiotemporal progress of degeneration/regeneration in the silicone chamber model for nerve regeneration. Rat sciatic nerves were transected and the proximal and distal stumps were inserted into a bridging sili...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1993-03-01 00:00:00