Abstract:
:Proteasomal dysfunction has been recently implicated in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease and diffuse Lewy body disease. We have developed an in vitro model of proteasomal dysfunction by applying pharmacological inhibitors of the proteasome, lactacystin or ZIE[O-tBu]-A-leucinal (PSI), to dopaminergic PC12 cells. Proteasomal inhibition caused a dose-dependent increase in death of both naive and neuronally differentiated PC12 cells, which could be prevented by caspase inhibition or CPT-cAMP. A percentage of the surviving cells contained discrete cytoplasmic ubiquitinated inclusions, some of which also contained synuclein-1, the rat homologue of human alpha-synuclein. However the total level of synuclein-1 was not altered by proteasomal inhibition. The ubiquitinated inclusions were present only within surviving cells, and their number was increased if cell death was prevented. We have thus replicated, in this model system, the two cardinal pathological features of Lewy body diseases, neuronal death and the formation of cytoplasmic ubiquitinated inclusions. Our findings suggest that inclusion body formation and cell death may be dissociated from one another.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Rideout HJ,Larsen KE,Sulzer D,Stefanis Ldoi
10.1046/j.1471-4159.2001.00474.xkeywords:
subject
Has Abstractpub_date
2001-08-01 00:00:00pages
899-908issue
4eissn
0022-3042issn
1471-4159journal_volume
78pub_type
杂志文章abstract:UNLABELLED:J. Neurochem. (2012) 121, 597-606. ABSTRACT:In cultured rat neocortical interneurons, we have studied the effect of long-term application of NMDA or AMPA on the surface density of the NMDA (GluN) receptor subunits GluN1 and GluN2B. Stimulation of Ca(2+) -permeable AMPA (GluA) receptors located on the intern...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2012.07719.x
更新日期:2012-05-01 00:00:00
abstract::Challenge of protease-activated receptors induces cytosolic Ca(2+) concentration ([Ca(2+) ](c)) increase, mitogen-activated protein kinase activation and reactive oxygen species (ROS) formation with a bandwidth of responses in individual cells. We detected in this study in situ the thrombin-induced [Ca(2+) ](c) rise a...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07527.x
更新日期:2011-12-01 00:00:00
abstract::Pilocarpine-induced seizures are mediated by the M(1) subtype of muscarinic acetylcholine receptor (mAChR), but little is known about the signaling mechanisms linking the receptor to seizures. The extracellular signal-regulated kinase (ERK) signaling cascade is activated by M(1) mAChR and is elevated during status epi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.00977.x
更新日期:2002-07-01 00:00:00
abstract::Increasing reports support that air pollution causes neuroinflammation and is linked to central nervous system (CNS) disease/damage. Diesel exhaust particles (DEP) are a major component of urban air pollution, which has been linked to microglial activation and Parkinson's disease-like pathology. To begin to address ho...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12231
更新日期:2013-06-01 00:00:00
abstract::Schwannoma-derived growth factor (SDGF) is a potent mitogen and neuronal differentiation factor. Because of its relationship to epidermal growth factor (EGF) and the heregulins, it was asked if SDGF interacts with the EGF receptor or HER2/neu. SDGF binds to and causes the phosphorylation on tyrosine of the EGF recepto...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.65041895.x
更新日期:1995-10-01 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disorder that represents the most common type of dementia among elderly people. Amyloid beta (Aβ) peptides in extracellular Aβ plaques, produced from the amyloid precursor protein (APP) via sequential processing by β- and γ-secretases, impair hippocampal synaptic plastic...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12728
更新日期:2014-08-01 00:00:00
abstract::The ontogeny of muscarinic receptors was studied in human fetal striatum, brainstem, and cerebellum to investigate general principles of synaptogenesis as well as the physiological balance between various chemical synapses during development in a given region of the brain. [3H]Quinuclidinyl benzilate ([3H]QNB) binding...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb10555.x
更新日期:1985-12-01 00:00:00
abstract::The in vitro and in vivo performance of three different semipermeable microdialysis membranes was compared: a proprietary polycarbonate-ether membrane made by Carnegie Medecin; cuprophan, a regenerated cellulose membrane; and polyacrylonitrile. When microdialysis probes were tested in a stirred in vitro solution, larg...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb01982.x
更新日期:1990-04-01 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 binding of a series of glycosylated beta-galactosidases to a fraction rich in synaptic membrane of bovine brain was examined. beta-galactosidase modified with p-aminophenyl beta-D-galactopyranoside (beta-D-Gal beta-gal) was found the most effective in binding to synaptic membrane, followed by that modified with be...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb13018.x
更新日期:1986-02-01 00:00:00
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
doi:10.1111/j.1471-4159.1992.tb08895.x
更新日期:1992-07-01 00:00:00
abstract::Action mechanism of lipopolysaccharide (LPS), interleukin-1β (IL-1β), and lysophosphatidic acid (LPA) to regulate motility, an important process of astrogliosis, was investigated in rat astrocytes. While LPA exerted no significant effect on the cell migration, the prior treatment of the cells with LPS or IL-1β resulte...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07188.x
更新日期:2011-04-01 00:00:00
abstract::P25alpha is a protein normally expressed in oligodendrocytes and subcellular relocalization of p25alpha occurs in multiple system atrophy, Parkinson's disease and Lewy body dementia along with ectopic expression in neurons. Moreover, it accumulates in Lewy body inclusions with aggregated alpha-synuclein and is a poten...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05437.x
更新日期:2008-07-01 00:00:00
abstract::Neuropathic pain is a debilitating chronic pain condition occurring after damage in the nervous system and is refractory to the currently available treatments. Major challenges include elucidating its mechanisms and developing new medications to treat it. Nerve injury-induced pain hypersensitivity involves aberrant ex...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/jnc.14001
更新日期:2017-05-01 00:00:00
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
更新日期:1991-03-01 00:00:00
abstract::Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract near the C-terminus of the MJD-1 gene product, ataxin-3. Ataxin-3 is degraded by the proteasome. However, the precise mechanism of ataxin-3 degradation remains to be elucidated. In this st...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04460.x
更新日期:2007-06-01 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::Manganese is an essential nutrient, integral to proper metabolism of amino acids, proteins and lipids. Excessive environmental exposure to manganese can produce extrapyramidal symptoms similar to those observed in Parkinson's disease (PD). We used in vivo and in vitro models to examine cellular and circuitry alteratio...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2009.06145.x
更新日期:2009-07-01 00:00:00
abstract::Plasma osmolality and the levels of water, taurine, and total amino nitrogen (detected as ninhydrin-positive substances) have been measured in the cerebral cortices of nonpregnant and 19-day pregnant Wistar rats. Plasma osmolality fell by 11 mosmol/kg during pregnancy. Brain water content remained unaltered, but level...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb07328.x
更新日期:1989-07-01 00:00:00
abstract::Neuroprotection is one of the prominent functions of the interleukin (IL)-6-type cytokine family, for which the underlying mechanism(s) are not fully understood. We have previously shown that neuroprotection and neuromodulation mediated by IL-6 require neuronal adenosine A(1) receptor (A(1) R) function. We now have in...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06881.x
更新日期:2010-09-01 00:00:00
abstract::Calmodulin regulated spectrin-associated protein 1 (CAMSAP1) is a vertebrate microtubule-binding protein, and a representative of a family of cytoskeletal proteins that arose with animals. We reported previously that the central region of the protein, which contains no recognized functional domain, inhibited neurite o...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12462
更新日期:2014-02-01 00:00:00
abstract::Stimulated dopamine overflow has been measured with in vivo voltammetry in the caudate-putamen and nucleus accumbens. Overflow was induced by electrical stimulation of the medial forebrain bundle with 120 1-ms, 300-microA, biphasic pulses at frequencies between 10 and 60 Hz. Overflow was measured with a Nafion-coated,...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb11789.x
更新日期:1989-09-01 00:00:00
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
doi:10.1046/j.1471-4159.1994.62062241.x
更新日期:1994-06-01 00:00:00
abstract::Previous studies examining age differences in membrane fluidity and cholesterol content have reported on the average or total change in membrane structure, respectively. However, a membrane consists of an exofacial leaflet and a cytofacial leaflet that differ in fluidity and cholesterol distribution. The purpose of th...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.66041717.x
更新日期:1996-04-01 00:00:00
abstract::Genomic and cDNA clones encoding the rat D1 receptor were isolated and sequenced. Comparison of the D1 receptor cDNA and genomic sequences revealed that the rat D1 receptor gene is organized into two exons separated by a small intron in the 5' untranslated region of its mRNA. The transcription start site is located 86...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb11023.x
更新日期:1992-11-01 00:00:00
abstract::Exposure of neurones in culture to excitotoxic levels of glutamate results in an initial transient spike in [Ca2+]i followed by a delayed, irreversible [Ca2+]i rise governed by rapid kinetics, with Ca2+ originating from the extracellular medium. The molecular mechanism responsible for the secondary Ca2+ rise is unknow...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02732.x
更新日期:2004-10-01 00:00:00
abstract::The changes of glutathione S-transferase activity were investigated using rat brain astroglioma C6 cells that were synchronized at different phases of the cell cycle. The enzyme showed two significant activity peaks at G2 and G1 phases. Furthermore, when C6 glioma cells were exposed to a culture medium supplemented wi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb13244.x
更新日期:1988-01-01 00:00:00
abstract::The decrease of pyruvate and ketoglutarate dehydrogenase complex activities is the main cause of energy and acetyl-CoA deficits in thiamine deficiency-evoked cholinergic encephalopathies. However, disturbances in pathways of acetyl-CoA metabolism leading to appearance of cholinergic deficits remain unknown. Therefore,...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06919.x
更新日期:2010-10-01 00:00:00
abstract::Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) share common components in their multimeric receptors. Both cytokine receptors contain gp130/interleukin-6-receptor transducer as well as gp190/low affinity LIF receptor. For CNTF, addition of a third subunit, or alpha subunit, defines the high-af...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.66041391.x
更新日期:1996-04-01 00:00:00
abstract::Inhalation of either 0.5% or 1.0% halothane in air caused a slight decrease in the cAMP concentration in rat cerebral cortex and cerebellum. During recovery, concentrations returned to normal in 3 h, or less. In contrast, cGMP decreased sixfold in cerebellum, but increased twofold in cortex. Recovery time for cerebell...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb06298.x
更新日期:1980-08-01 00:00:00