Abstract：
:Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate. Only in the animal kingdom is this enzyme heavily allosterically regulated by a wide array of metabolites. The major activators are ADP and leucine and inhibitors include GTP, palmitoyl CoA, and ATP. Spontaneous mutations in the GTP inhibitory site that lead to the hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as to why mammalian GDH is so tightly regulated. Patients with HHS exhibit hypersecretion of insulin upon consumption of protein and concomitantly extremely high levels of ammonium in the serum. The atomic structures of four new inhibitors complexed with GDH complexes have identified three different allosteric binding sites. Using a transgenic mouse model expressing the human HHS form of GDH, at least three of these compounds blocked the dysregulated form of GDH in pancreatic tissue. EGCG from green tea prevented the hyper-response to amino acids in whole animals and improved basal serum glucose levels. The atomic structure of the ECG-GDH complex and mutagenesis studies is directing structure-based drug design using these polyphenols as a base scaffold. In addition, all of these allosteric inhibitors are elucidating the atomic mechanisms of allostery in this complex enzyme.
journal_name
Neurochem Resjournal_title
Neurochemical researchauthors
Li M,Li C,Allen A,Stanley CA,Smith TJdoi
10.1007/s11064-013-1173-2subject
Has Abstractpub_date
2014-01-01 00:00:00pages
433-45issue
3eissn
0364-3190issn
1573-6903journal_volume
39pub_type
杂志文章,评审abstract：:The neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are both expressed in developing cerebellum in addition to their tyrosine kinase receptors. TrkB and TrkC. In contrast to BDNF.NT-3 has only a negligible or a transient survival activity on cultured cerebellar granule neurons. The gra...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF02532309
更新日期：1996-07-01 00:00:00
abstract：:The expression and localization of syntaxin isoforms 1A and 1B in adrenergic and noradrenergic chromaffin cells were examined by both immunoblot analysis and confocal immunofluorescence microscopy. Syntaxin 1A was found in higher levels in noradrenergic cells, whereas syntaxin 1B was similarly expressed in most noradr...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1023/a:1025658005937
更新日期：2003-10-01 00:00:00
abstract：:Radioactive azide derivatives of tetrodotoxin (TTX) were synthesized using 2-nitro-4-azidephenyl-[3H]beta alanine for the purpose of photolabeling of the Na channel. Three azide derivatives, N1, N2 and N3, were separated by ion exchange chromatography on Bio-Rex 70 resin and reversed phase high performance liquid chro...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965886
更新日期：1985-08-01 00:00:00
abstract：:Neuronal perikarya were isolated, using bulk preparative procedures, from bovine brains. Synaptosomes, neuronal perikarya, and brain homogenates had similar ganglioside patterns, with the synaptosomes containing at least four times more total ganglioside per mg protein than the neuronal perikarya and twice that of the...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00966108
更新日期：1976-04-01 00:00:00
abstract：:Rat obturator nerve 16S acetylcholinesterase (16S AChE) was separated by sucrose gradient velocity sedimentation and compared to the 16S form of AChE similarly derived from endplate regions of anterior gracilis muscles. The 16S AChE from both tissues could only be extracted in high ionic strength buffer; as it aggrega...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965031
更新日期：1981-09-01 00:00:00
abstract：:Neonatal hypoxia/ischemia (HI) is the most common cause of developmental neurological, cognitive and behavioral deficits in children, with hyperoxia (HHI) treatment being a clinical therapy for newborn resuscitation. Although cerebral edema is a common outcome after HI, the mechanisms leading to excessive fluid accumu...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-010-0308-y
更新日期：2010-12-01 00:00:00
abstract：:The purpose of this study was to investigate whether the kappa-opioid receptor (KOR) agonist, BRL52537, has a neuroprotective effect against cerebral ischemia/reperfusion (I/R) injury in rats and further explore the underlying mechanisms. Adult male Sprague-Dawley rats were randomly assigned into sham (group A), I/R (...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-013-1139-4
更新日期：2013-11-01 00:00:00
abstract：:The study examined (a) whether there is sex difference in spinal cord and plasma oxidative stress profiles in Dark Agouti rats immunised for experimental autoimmune encephalomyelitis (EAE), the principal experimental model of multiple sclerosis, and (b) whether there is correlation between the oxidative stress in spin...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-016-2094-7
更新日期：2017-02-01 00:00:00
abstract：:The features of neuronal damage induced by the mitochondrial toxin NaN(3) were investigated in rat primary cortical neuron cultures. Cell viability (MTT colorimetric determination) and transmembrane mitochondrial potential (J-C1 fluorescence) were concentration-dependently reduced 24 h after NaN(3); neither nuclear fr...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-008-9852-0
更新日期：2009-05-01 00:00:00
abstract：:Metabolic modeling of dynamic (13)C labeling curves during infusion of (13)C-labeled substrates allows quantitative measurements of metabolic rates in vivo. However metabolic modeling studies performed in the brain to date have only modeled time courses of total isotopic enrichment at individual carbon positions (posi...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-012-0782-5
更新日期：2012-11-01 00:00:00
abstract：:Methylguanidine (MG) is known as not only a nephrotoxin but also as a neurotoxine. We have previously showed that MG itself generates hydroxyl radicals (*OH) in an in vitro study. In this study, we examined the inhibitory effects of ascorbate, EPC-K(1) (alpha-tocopheryl-L-ascorbate-2-O-phosphate diester), Trolox (wate...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-008-9811-9
更新日期：2009-04-01 00:00:00
abstract：:Endogenous and xenobiotic sulphur-containing convulsant and non-convulsant compounds containing structural moieties of, or bearing a structural resemblance to, GABA and homocysteine were tested in binding studies for their potency in displacing the GABA-mimetic [3H]muscimol from specific, high-affinity sites (Kd = 3.6...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00971006
更新日期：1987-07-01 00:00:00
abstract：:The mitochondrial enzyme, pyruvate carboxylase (PC; EC 6.4.1.1) is considered to play a significant role in the intermediary metabolism of neural tissue. PC-catalyzed carboxylation of pyruvate to oxaloacetate is a major anaplerotic reaction in brain. Anaplerosis is essential for homeostasis of the members of the trica...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-008-9806-6
更新日期：2009-03-01 00:00:00
abstract：:Omega-conotoxin GVIA (omega-CTX), as a selective blocker for an N-type Ca2+ channel, has been conveniently used in many molecular biochemical and pharmacological experiments. There has been little elucidation of 125I-omega-CTX binding sites (mainly the 135-kDa band) in the crude membranes from chick brain, although th...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1023/a:1022805615926
更新日期：2003-05-01 00:00:00
abstract：:Status epilepticus is a common manifestation of nerve agent toxicity and represents a serious medical emergency with high rates of mortality and neurologic injury in those that survive. The aim of the current study was to determine if targeting oxidative stress with the catalytic antioxidant, AEOL10150, would reduce p...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-017-2273-1
更新日期：2017-07-01 00:00:00
abstract：:Brief limb ischemia was reported to protect neurons against injury induced by subsequent cerebral ischemia-reperfusion, and this phenomenon is known as limb ischemic preconditioning (LIP). To explore the role of nitric oxide (NO) in neuroprotection of LIP in rats, we observed changes in the content of nitric oxide (NO...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-007-9381-2
更新日期：2007-11-01 00:00:00
abstract：:Interleukin (IL)-18, a member of the IL-1 cytokine family, is an important mediator of peripheral inflammation and host defence responses. However, although IL-1 is a key proinflammatory cytokine in the brain, little is known about IL-18 changes in glial cells under excitotoxic neurodegeneration. In this study, we cha...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-007-9434-6
更新日期：2008-01-01 00:00:00
abstract：:Shape-shifting, a phenomenon wide-spread in folklore, refers to the ability to physically change from one identity to another, typically from an innocuous entity to a destructive one. The amino acid D-serine over the last 25 years has "shape-shifted" into several identities: a purported glial transmitter activating N-...
journal_title：Neurochemical research
pub_type： 杂志文章,评审
doi：10.1007/s11064-020-03014-1
更新日期：2020-06-01 00:00:00
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journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00967701
更新日期：1994-06-01 00:00:00
abstract：:Ellagic acid (EA, 2,3,7,8-tetrahydroxy-chromeno; C14H6O8) is a polyphenol derived from fruits (pomegranates, berries) and nuts. EA exhibits antioxidant capacity and induces anti-inflammatory actions in several mammalian tissues. EA has been characterized as a possible neuroprotective agent, but the number of reports i...
journal_title：Neurochemical research
pub_type： 杂志文章,评审
doi：10.1007/s11064-016-1853-9
更新日期：2016-06-01 00:00:00
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journal_title：Neurochemical research
pub_type： 杂志文章,评审
doi：10.1007/s11064-008-9711-z
更新日期：2008-10-01 00:00:00
abstract：:Disturbance in cholesterol homeostasis appears to be an important factor in the pathogenesis of neurodegenerative disorders. The aim of the present study was to investigate sterol regulatory element binding protein (SREBP) levels in the nuclear extracts of human neuroblastoma cells and the possible interaction of beta...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-008-9832-4
更新日期：2009-05-01 00:00:00
abstract：:The characteristics of endogenous Ca2+/calmodulin (CaM)- and Ca2+/phosphatidylserine (PS)-stimulated phosphorylated proteins in the striatum of rat were partially determined and compared in this study. The Ca2+/CaM-dependent phosphoproteins were associated with serine and threonine residues. The sensitivity of these p...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00968670
更新日期：1990-03-01 00:00:00
abstract：:The tyrosine phosphatase inhibitor BpV(phen) stimulated a concentration-dependent increase of phospholipase C (PLC) activity in bovine adrenal medullary chromaffin cells. This response was accompanied by an increase in PLCgamma1 tyrosine phosphorylation and its cytosketetal translocation. Insulin, at high concentratio...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1023/b:nere.0000042211.76499.c6
更新日期：2004-10-01 00:00:00
abstract：:Tau is a protein involved in regulation of microtubule stability, axonal differentiation and transport. Alteration of retrograde transport may lead to motor neuron degeneration. Thus alternative mRNA splicing and expression of tau isoforms were studied in a transgenic mouse model harboring the human SOD1 G93A mutation...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-006-9057-3
更新日期：2006-05-01 00:00:00
abstract：:Cold restraint stress (CRS) model exerts similar effect as physiological stress because it combines emotional stress (escape reaction) and physical stress (muscle work). It is well established that various responses to stress are regulated by sympathoadrenal system, brain monoaminergic systems and oxidative processes....
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-012-0867-1
更新日期：2012-12-01 00:00:00
abstract：:To assess RNAi mediated inhibition of the expression of wt-DYT1 on H(2)O(2)-induced toxicity in NIH 3T3 cells and primary cortical neurons. To detect the function of wild-type Torsin A and the effect of SiRNA on the wt-DYT1 gene. The shRNA expression vector was constructed by ligating annealed complementary shRNA olig...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-010-0177-4
更新日期：2010-08-01 00:00:00
abstract：:Previous studies have shown that early life stress induced by maternal separation or non-handling can lead to behavioural deficits in rats and that these deficits can be alleviated by providing palatable cafeteria high-fat diet (HFD). In these studies we investigated the effects of maternal separation or non-handling ...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-013-0985-4
更新日期：2013-04-01 00:00:00
abstract：:Although nitric oxide (NO) plays key signaling roles in the nervous systems, excess NO leads to cell death. In this study, the involvement of p38 mitogen-activated protein kinase (p38 MAPK) and apoptosis signal-regulating kinase-1 (ASK1) in NO-induced cell death was investigated in PC12 cells. NO donor transiently act...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1023/a:1010917129951
更新日期：2001-05-01 00:00:00
abstract：:We estimated catecholamine levels in CSF of 15 epileptics and 75 non-neurological patients utilizing a high performance liquid chromatograph with a highly sensitive fluorometer and found the following results: The dopamine (DA) levels in males were significantly higher than those in females, while norepinephrine (NE) ...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965900
更新日期：1982-10-01 00:00:00
