Abstract：
:The GLS1 gene encodes a mitochondrial glutaminase that is highly expressed in brain, kidney, small intestine and many transformed cells. Recent studies have identified multiple lysine residues in glutaminase that are sites of N-acetylation. Interestingly, these sites are located within either a loop segment that regulates access of glutamine to the active site or the dimer:dimer interface that participates in the phosphate-dependent oligomerization and activation of the enzyme. These two segments also contain the binding sites for bis-2[5-phenylacetamido-1,2,4-thiadiazol-2-yl]ethylsulfide (BPTES), a highly specific and potent uncompetitive inhibitor of this glutaminase. BPTES is also the lead compound for development of novel cancer chemotherapeutic agents. To provide a preliminary assessment of the potential effects of N-acetylation, the corresponding lysine to alanine mutations were constructed in the hGACΔ1 plasmid. The wild type and mutated proteins were purified by Ni(+)-affinity chromatography and their phosphate activation and BPTES inhibition profiles were analyzed. Two of the alanine substitutions in the loop segment (K311A and K328A) and the one in the dimer:dimer interface (K396A) form enzymes that require greater concentrations of phosphate to produce half-maximal activation and exhibit greater sensitivity to BPTES inhibition. By contrast, the K320A mutation results in a glutaminase that exhibits near maximal activity in the absence of phosphate and is not inhibited by BPTES. Thus, lysine N-acetylation may contribute to the acute regulation of glutaminase activity in various tissues and alter the efficacy of BPTES-type inhibitors.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
McDonald CJ,Acheff E,Kennedy R,Taylor L,Curthoys NPdoi
10.1016/j.neuint.2014.12.003subject
Has Abstractpub_date
2015-09-01 00:00:00pages
10-4eissn
0197-0186issn
1872-9754pii
S0197-0186(14)00250-2journal_volume
88pub_type
杂志文章abstract：:Whereas carbachol, noradrenaline, serotonin and memantine stimulated inositol phosphates production and calcium mobilization in 3-5 day old rabbit retinal cultures, only carbachol and noradrenaline were effective when 25-30 day old cultures were used. The older retinal cultures contain only Müller cells which shows th...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(92)90183-r
更新日期：1992-10-01 00:00:00
abstract：:The roles of cyclic AMP and calcium in the regulation of serotonin N-acetyltransferase (NAT) activity were studied in low density monolayer cultures of chick retinal photoreceptors and neurons. Photoreceptor-enriched retinal cell cultures were prepared from embryonic day 6 retinas and cultured for 6 days. NAT activity...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(95)00035-7
更新日期：1995-08-01 00:00:00
abstract：:Oxidative stress (OS) has been related to cocaine's actions and also to numerous nervous system pathologies, including seizures. The purpose of this work was to determine the alterations in glutathione (GSH) content, nitrite/nitrate and MDA levels after cocaine-induced toxicity. Male Swiss mice were injected (i.p.) wi...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2009.10.001
更新日期：2010-01-01 00:00:00
abstract：:The discovery of nonsynaptic communication in the 1960s and 1970s was an important milestone in investigating the function of the nervous system, and it revolutionized our view about information transmission between neurons. In addition, nonsynaptic communication has a practical importance not only within the nervous ...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2007.06.001
更新日期：2008-01-01 00:00:00
abstract：:The present studies were performed in order to examine the possible role of cyclic GMP-stimulated phosphodiesterase (cGMP-PDE) activity in the inhibitory action of the inflammatory peptide bradykinin on cyclic AMP (cAMP) accumulation in D384 cells. Bradykinin decreased the forskolin-stimulated cAMP accumulation in the...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(92)90149-l
更新日期：1992-09-01 00:00:00
abstract：:Even though the inducing effect of electromagnetic fields (EMF) on the neural differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) is a distinctive, the underlying mechanism of differentiation remains unclear. To find out the signaling pathways involved in the neural differentiation of BM-MSCs by EMF...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2013.02.002
更新日期：2013-03-01 00:00:00
abstract：:Rat brain membranes were incubated with bee venom phospholipase A(2) (PLA(2)) or phospholipase C (PLC) from Clostridium perfringens. PLA(2) caused a significant increase in free polyunsaturated fatty acids concomitant with membrane phospholipid degradation as monitored by HPLC and by gas chromatography. Equal concentr...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(87)90104-5
更新日期：1987-01-01 00:00:00
abstract：:The molecular mechanism responsible for hyperphosphorylated tau accumulation in dendrites of Alzheimer's disease (AD) neurons has not been fully clarified. Recently, we reported that tau mRNA is distributed into dendrites, and that translation and phosphorylation of tau protein are immediately enhanced in response to ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2020.104808
更新日期：2020-10-01 00:00:00
abstract：:Arsenate is a toxic compound that has been connected with neuropathies and impaired cognitive functions. To test whether arsenate affects the viability and the GSH metabolism of brain astrocytes, we have used primary astrocyte cultures as model system. Incubation of astrocytes for 2h with arsenate in concentrations of...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2013.03.014
更新日期：2013-06-01 00:00:00
abstract：:The inflammatory central nervous system response that involves activated microglia and reactive astrocytes may both heal and harm neurons, as inflammatory mediators lead to neuroprotection or excitation at one dose but to injury at a different concentration. To investigate these complex cellular interactions, L-trans-...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2006.06.008
更新日期：2006-12-01 00:00:00
abstract：:Age, sex, and gonadal hormones have profound effects on ischemic stroke outcomes, although how these factors impact basic stroke pathophysiology remains unclear. There is a plethora of inconsistent data reported throughout the literature, primarily due to differences in the species examined, the timing and methods use...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2012.10.003
更新日期：2012-12-01 00:00:00
abstract：:Chronic ingestion of caffeine causes dependence and sleep disturbance in children and adolescents. In rodents, the administration of caffeine may produce behavioral cross-sensitization to some psychostimulants, such as dopaminergic psychoactive drugs. Methylphenidate (MPH; Ritalin) is a psychostimulant used in pediatr...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2009.03.015
更新日期：2009-09-01 00:00:00
abstract：:Synaptic degeneration is one of the earliest hallmarks of Alzheimer disease (AD) and results in loss of cognitive function. One of the causative agents for the synaptic degeneration is the amyloid β-peptide (Aβ), which is formed from its precursor protein by two sequential cleavages mediated by β- and γ-secretase. We ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2012.03.016
更新日期：2012-07-01 00:00:00
abstract：:Posttranslational processing of peptide-precursors is nowadays believed to play an important role in the functioning of neurons and endocrine cells. Both proenkephalins and chromogranins/secretogranins are considered as precursor molecules in these tissues, resulting in posttranslationally formed degradation products ...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/0197-0186(93)90016-x
更新日期：1993-04-01 00:00:00
abstract：:It has been reported that mutations of gammaPKC cause hereditary spinocerebellar atrophy type 14 (SCA14). Our recent study has revealed that the SCA14 mutant gammaPKC is susceptible to aggregation and causes cell death. Among mutations/polymorphisms of gammaPKC, the R659S mutation was firstly segregated from families ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2006.05.005
更新日期：2006-12-01 00:00:00
abstract：:The effects of hypoxia on the metabolism of the central nervous system were investigated in rats submitted to a low oxygen atmosphere (8% O(2); 92% N(2)). [1-(13)C]glucose and [2-(13)C]acetate were used as substrates, this latter being preferentially metabolized by glial cells. After 1-h substrate infusion, the incorp...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(00)00106-6
更新日期：2001-04-01 00:00:00
abstract：:Adenosine exerts two parallel modulatory roles in the CNS, acting as a homeostatic modulator and also as a neuromodulator at the synaptic level. We will present evidence to suggest that these two different modulatory roles are fulfilled by extracellular adenosine originated from different metabolic sources, and involv...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/s0197-0186(00)00034-6
更新日期：2001-02-01 00:00:00
abstract：:Astrocytes, besides supporting metabolic and scaffolding functions, play a prominent role in the modulation of neuronal communication. In particular, they are responsible for clearing synaptically-released glutamate via highly specific transporters located on their plasma membrane. Since glutamate is the main excitato...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2003.07.005
更新日期：2004-07-01 00:00:00
abstract：:Glutaminase mediates the recycling of neurotransmitter glutamate, supporting most excitatory neurotransmission in the mammalian central nervous system. A constitutive heterozygous reduction in GLS1 engenders in mice a model of schizophrenia resilience and associated increases in Gln, reductions in Glu and activity-dep...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2019.104508
更新日期：2019-10-01 00:00:00
abstract：:Excitotoxicity is the main event during neurological disorders producing drastic morphological and functional changes. Rac-GTPase is involved in cytoskeletal remodeling and survival. However, the role of Rac1 after cerebral ischemia has not been completely understood yet. In this study, we evaluated the activity of Ra...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2010.08.014
更新日期：2010-12-01 00:00:00
abstract：:In the last few years, several attempts were made for the setting up of specific methodologies aiming to evaluate steroid contents directly in nervous tissues. The main objective of these attempts was to determine accurately changes intervening in endogenous neuroactive steroid levels during pathological situations. T...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2007.09.010
更新日期：2008-03-01 00:00:00
abstract：:Conventional kinetic models of brain glucose uptake and metabolism that visualize brain glucose as being in a single pool in equilibrium with plasma, are unable to account for some recently described experimental findings. These include microdialysis demonstrations of a brain extracellular fluid glucose concentration ...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/0197-0186(95)00094-1
更新日期：1996-03-01 00:00:00
abstract：:This study was aimed at examining the effect of tamoxifen, a selective estrogen receptor modulator, on the release of endogenous glutamate in rat cerebral cortex nerve terminals (synaptosomes) and exploring the possible mechanism. Tamoxifen inhibited the release of glutamate that was evoked by the K(+) channel blocker...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2011.11.014
更新日期：2012-01-01 00:00:00
abstract：:Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in ami...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2005.12.037
更新日期：2006-05-01 00:00:00
abstract：:Glial scar is a major impediment to axonal regeneration in central nervous system (CNS) disorders. Overcoming this physical and biochemical barrier might be crucial for axonal regeneration and functional compensation during the progression of CNS disorders. The mammalian target of rapamycin (mTOR) is an evolutionarily...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2015.03.001
更新日期：2015-04-01 00:00:00
abstract：:Parkinson's disease (PD) is a progressive and debilitating neurodegenerative disorder that affects over one million people in the United States. Previous studies, carried out in young adult rats, have shown that calcitriol, the active metabolite of vitamin D, can be neuroprotective in 6-hydroxydopamine (6-OHDA) models...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2017.04.001
更新日期：2017-09-01 00:00:00
abstract：:Synaptic like microvesicles (SLMV) form a pleiomorphic population of vesicles present in neuroendocrine cells of the pituitary and the adrenal medulla. Their composition and biogenesis is very similar to small synaptic vesicles (SSV) present in nerve terminals. Membrane proteins of SSV involved in fusion (synaptotagmi...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/0197-0186(95)00005-s
更新日期：1995-09-01 00:00:00
abstract：:Retinal melatonin biosynthesis is regulated in part by changes in the activity of serotonin N-acetyltransferase (NAT), which increases at night in dark-adapted retinas, but not in light-exposed retinas. Using an in vitro preparation of Xenopus laevis (African clawed frog) eye cups, we have obtained evidence supporting...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(89)90174-5
更新日期：1989-01-01 00:00:00
abstract：:NADPH derived from glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, has been implicated not only to promote reduced glutathione (GSH) but also enhance oxidative stress in specific cellular conditions. In this study, the effects of G6PD antisense oligodeoxynucleotides...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2012.05.003
更新日期：2012-07-01 00:00:00
abstract：:An intraocular injection of [(3)H]proline was used to label rabbit retinal ganglion cells including components subjected to axonal transport. Degradation of rapidly axonally transported labelled proteins was estimated in an in vitro system using homogenates of the nerve terminal regions. The energy requirements of thi...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(85)90061-0
更新日期：1985-01-01 00:00:00
