Abstract：
:Cyclin-dependent kinase 5 (Cdk5) is emerging as a neuronal protein kinase involved in multiple aspects of neurotransmission in both post- and presynaptic compartments. Within the reward/motor circuitry of the basal ganglia, Cdk5 regulates dopamine neurotransmission via phosphorylation of the postsynaptic signal transduction pathway integrator, DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein, M(r) 32,000). Cdk5 has also been implicated in regulating various steps in the presynaptic vesicle cycle. Here we report that Cdk5 phosphorylates tyrosine hydroxylase (TH), the key enzyme for synthesis of dopamine. Using phosphopeptide mapping, site-directed mutagenesis, and phosphorylation state-specific antibodies, the site was identified as Ser31, a previously defined extracellular signal-regulated kinases 1/2 (ERK1/2) site. The phosphorylation of Ser31 by Cdk5 versus ERK1/2 was investigated in intact mouse striatal tissue using a pharmacological approach. The results indicated that Cdk5 phosphorylates TH directly and also regulates ERK1/2-dependent phosphorylation of TH through the phosphorylation of mitogen-activated protein kinase kinase 1 (MEK1). Finally, phospho-Ser31 TH levels were increased in dopaminergic neurons of rats trained to chronically self-administer cocaine. These results demonstrate direct and indirect regulation of the phosphorylation state of a Cdk5/ERK1/2 site on TH and suggest a role for these pathways in the neuroadaptive changes associated with chronic cocaine exposure.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Kansy JW,Daubner SC,Nishi A,Sotogaku N,Lloyd MD,Nguyen C,Lu L,Haycock JW,Hope BT,Fitzpatrick PF,Bibb JAdoi
10.1111/j.1471-4159.2004.02723.xkeywords:
subject
Has Abstractpub_date
2004-10-01 00:00:00pages
374-84issue
2eissn
0022-3042issn
1471-4159pii
JNC2723journal_volume
91pub_type
杂志文章abstract：:1-[2-(4-Aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (PAPP) inhibits [3H]5-hydroxytryptamine (5-HT, serotonin) binding to 5-HT1A and 5-HT1B sites in rat brain with apparent equilibrium dissociation constants (KD) of 2.9 and 328 nM, respectively. [3H]PAPP was synthesized, its binding to central serotonin re...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb12926.x
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abstract：:Purified tribulin, an endogenous monoamine oxidase (MAO) inhibitor, has been identified by direct probe insertion mass spectrometry as the indole-2,3-dione, isatin. A gas chromatographic-mass spectrometric assay for isatin has been developed and used to measure its relatively high concentrations in unpurified human ur...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb01089.x
更新日期：1988-08-01 00:00:00
abstract：:It has been suggested that disturbances during neurodevelopment may play a crucial role in the etiology of schizophrenia (SZ). This premise is supported by brain imaging, epidemiological, and pathological studies as well as the discovery of susceptibility genes for SZ that appear to be implicated in development of the...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/j.1471-4159.2007.04628.x
更新日期：2007-08-01 00:00:00
abstract：:Apoptotic cell death has been proposed to play a role in the neuronal loss observed following traumatic injury in the CNS and PNS. The present study uses an in vitro tissue culture model to investigate whether free fatty acids (FFAs), at concentrations comparable to those found following traumatic brain injury, trigge...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01571.x
更新日期：2003-02-01 00:00:00
abstract：:Variations occurring in cortical nitric oxide (NO) release were analysed with a voltametric method in rats (i) placed in control conditions, (ii) while being paradoxical sleep deprived (PSD), or (iii) recovering from a PSD. Activities of neuronal (nNOS) and inducible (iNOS) NO-synthases as well as nNOS expression were...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02529.x
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abstract：:Neurofibrillary tangles (NFTs) consisting of the hyperphosphorylated microtubule-associated protein tau are a defining pathological characteristic of Alzheimer's disease (AD). Hyperphosphorylation of tau is hypothesized to impair the microtubule stabilizing function of tau, leading to the formation of paired helical f...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.02070.x
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abstract：:Most ingested ethanol is metabolized in the liver to acetaldehyde and then to acetate, which can be oxidized by the brain. This project assessed whether chronic exposure to alcohol can increase cerebral oxidation of acetate. Through metabolism, acetate may contribute to long-term adaptation to drinking. Two groups of ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12405
更新日期：2013-11-01 00:00:00
abstract：:Inhibition of the mitochondrial electron transport chain (ETC) ultimately limits ATP production and depletes cellular ATP. However, the individual complexes of the ETC in brain mitochondria need to be inhibited by approximately 50% before causing significant depression of ATP synthesis. Moreover, the ETC is the key si...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03374.x
更新日期：2005-10-01 00:00:00
abstract：:Post-traumatic immune suppression renders individuals with spinal cord injury (SCI) susceptible to infection. Normally, proper immune function is regulated by collaboration between the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis and involves the controlled release of glucocorticoids ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06232.x
更新日期：2009-09-01 00:00:00
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pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0750656.x
更新日期：2000-08-01 00:00:00
abstract：:Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-PHDs) are important targets against oxidative stress. We hypothesized that inhibition HIF-PHD by adaptaquin reduces hypoxic-ischemic brain injury in a neonatal mouse model. The pups were treated intraperitoneally immediately with adaptaquin after hypoxia-ischemia (HI...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.14790
更新日期：2019-09-01 00:00:00
abstract：:The nicotinic acetylcholine receptor (AChR) exhibits at least four different conformational states varying in affinity for agonists such as acetylcholine (ACh). Photoaffinity labeling has been previously used to elucidate the topography of the AChR. However, to date, the photosensitive probes used to explore the choli...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1996.67062557.x
更新日期：1996-12-01 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：:In the human fetus, obtained postmortem at estimated gestational ages of 8-22 weeks, biochemical activities of cortical choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were comparable to those of adult brain tissue. In contrast cholinergic receptor binding, including muscarinic M1 and M2 subtypes (mea...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb00749.x
更新日期：1986-10-01 00:00:00
abstract：:Alzheimer's disease (AD) belongs to one of the most multifactorial, complex and heterogeneous morbidity-leading disorders. Despite the extensive research in the field, AD pathogenesis is still at some extend obscure. Mechanisms linking AD with certain comorbidities, namely diabetes mellitus, obesity and dyslipidemia, ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/jnc.14256
更新日期：2018-02-01 00:00:00
abstract：:We assessed the effects of cold and isolation stress on arginine vasopressin (AVP) mRNA in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Vasopressin mRNA levels were determined by in situ hybridization histochemistry at the cellular level. In posterior magnocellular neurons of the PVN isol...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb03463.x
更新日期：1991-06-01 00:00:00
abstract：:Evidence of a link between aluminium and Alzheimer's disease, parkinsonism-dementia of Guam, and dialysis encephalopathy raises questions regarding the role of this element in the pathogenesis of these conditions. Therefore, we have investigated the use of gallium-67 (67Ga) as a marker for brain uptake of aluminium. T...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb08846.x
更新日期：1990-07-01 00:00:00
abstract：:Nitric oxide (NO) has been implicated in both the pathogenesis of and protection from NMDA receptor-mediated neuronal injury. This apparent paradox has been attributed to alternate redox states of nitrogen monoxide, whereby, depending on the redox milieu, nitrogen monoxide can be neuroprotective via nitrosation chemis...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0721843.x
更新日期：1999-05-01 00:00:00
abstract：:Synaptosomal-associated protein of 25 kDa (SNAP-25) is thought to play a key role in vesicle exocytosis and in the control of transmitter release. However, the precise mechanisms of action as well as the regulation of SNAP-25 remain unclear. Here we show by immunoprecipitation that activation of protein kinase C (PKC)...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.721699.x
更新日期：1999-04-01 00:00:00
abstract：:Agmatine (decarboxylated arginine) was originally identified in the CNS as an imidazoline receptor ligand. Further studies demonstrated that agmatine antagonizes NMDA receptors and inhibits nitric oxide synthase. Intrathecally administered agmatine inhibits opioid tolerance and hyperalgesia evoked by inflammation, ner...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04647.x
更新日期：2007-09-01 00:00:00
abstract：:Rats with unilateral lesions of the locus coeruleus were used to study the role of norepinephrine (NE) signal input in the down-regulation by antidepressants of the noradrenergic cyclic AMP-generating system in the cortex. Chronic administration of both desipramine (blockade of NE reuptake) and iprindole (no blockade ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb04739.x
更新日期：1982-07-01 00:00:00
abstract：:Injury-induced cytokines act through gp130 in sympathetic neurons to suppress expression of tyrosine hydroxylase (TH) and other genes associated with noradrenergic transmission. These cytokines also trigger the local loss of TH in peri-infarct sympathetic axons after myocardial infarction, but altered gene expression ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07539.x
更新日期：2012-01-01 00:00:00
abstract：:The presynaptic regulation of amino acid release from nerve terminals was investigated using synaptosomes prepared from the rat spinal cord. The basal releases of endogenous glutamate (Glu), aspartate (Asp), and gamma-amino-butyric acid (GABA) were 34.6, 21.5, and 10.0 pmol/min/mg of protein, respectively. Exposure to...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb03180.x
更新日期：1993-02-01 00:00:00
abstract：:Transgenic Huntington's disease (HD) mice, expressing exon 1 of the HD gene with an expanded CAG repeat, are totally resistant to striatal lesion induced by excessive NMDA receptor activation. We now show that striatal lesions induced by the mitochondrial toxin malonate are reduced by 70-80% in transgenic HD mice comp...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00482.x
更新日期：2001-08-01 00:00:00
abstract：:Metallothionein (MT)-III, a member of the MT family of metal-binding proteins, is mainly expressed in the CNS and is abundant in glutamatergic neurons. Results in genetically altered mice indicate that MT-III may play neuroprotective roles in the brain, but the mechanisms through which this protein functions have not ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0750266.x
更新日期：2000-07-01 00:00:00
abstract：:Neuroactive steroid family includes molecules synthesized in peripheral glands (i.e., hormonal steroids) and directly in the nervous system (i.e., neurosteroids) which are key regulators of the nervous function. As already reported in clinical and experimental studies, neurodegenerative diseases affect the levels of n...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12745
更新日期：2014-08-01 00:00:00
abstract：:Conditioned medium derived from a rat central nervous system neuronal cell line B104 (B104 CM) was shown previously to contain uncharacterized potent mitogen(s) for oligodendrocyte/type-2 astrocyte (O-2A) progenitor cells. In this study, we demonstrated that B104 cells produce and secrete platelet-derived growth facto...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.68062281.x
更新日期：1997-06-01 00:00:00
abstract：:We have previously demonstrated hippocampal hyperglutamatergic signaling occurs prior to plaque accumulation in AβPP/PS1 mice. Here, we evaluate 2-Amino-6-(trifluoromethoxy) benzothiazole (riluzole) as an early intervention strategy for Alzheimer's disease (AD), aimed at restoring glutamate neurotransmission prior to ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.15224
更新日期：2020-10-26 00:00:00
abstract：:This study demonstrates that in mammalian and nonmammalian species it is possible to deplete selectively and reversibly retinal glycinergic neurons of their content of glycine by exposure to sarcosine, a competitive inhibitor of glycine transporter 1 (glyt-1). This observation was used as a tool to test the hypothesis...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.70062628.x
更新日期：1998-06-01 00:00:00
abstract：:Although brain-derived neurotrophic factor is the most abundant and widely distributed neurotrophin in the nervous system, reproducible determinations of its levels have been hampered by difficulties in raising suitable monoclonal antibodies. Following immunization of mice with recombinant fish and mammalian brain-der...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0721930.x
更新日期：1999-05-01 00:00:00
