Abstract：
:Ligand-induced changes in the conformation of extracellular loop (EL) 2 in the rat (r) dopamine transporter (DAT) were examined using limited proteolysis with endoproteinase Asp-N and detection of cleavage products by epitope-specific immunoblotting. The principle N-terminal fragment produced by Asp-N was a 19kDa peptide likely derived by proteolysis of EL2 residue D174, which is present just past the extracellular end of TM3. Production of this fragment was significantly decreased by binding of cocaine and other uptake blockers, but was not affected by substrates or Zn(2+), indicating the presence of a conformational change at D174 that may be related to the mechanism of transport inhibition. DA transport activity and cocaine analog binding were decreased by Asp-N treatment, suggesting a requirement for EL2 integrity in these DAT functions. In a previous study we demonstrated that ligand-induced protease resistance also occurred at R218 on the C-terminal side of rDAT EL2. Here using substituted cysteine accessibility analysis of human (h) DAT we confirm cocaine-induced alterations in reactivity of the homologous R219 and identify conformational sensitivity of V221. Focused molecular modeling of D174 and R218 based on currently available Aquifex aeolicus leucine transporter crystal structures places these residues within 2.9Å of one another, suggesting their proximity as a structural basis for their similar conformational sensitivities and indicating their potential to form a salt bridge. These findings extend our understanding of DAT EL2 and its role in transport and binding functions.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Gaffaney JD,Shetty M,Felts B,Pramod AB,Foster JD,Henry LK,Vaughan RAdoi
10.1016/j.neuint.2013.11.003subject
Has Abstractpub_date
2014-07-01 00:00:00pages
16-26eissn
0197-0186issn
1872-9754pii
S0197-0186(13)00294-5journal_volume
73pub_type
杂志文章abstract：:Alzheimer's disease (AD) is a common neurodegenerative disorders, in which oxidative stress plays an important role. The present study investigated the effect of eicosapentaenoic acid-enriched phospholipids (EPA-enriched PL) from the sea cucumber Cucumaria frondosa on oxidative injury in PC12 cells induced by hydrogen...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2013.10.015
更新日期：2014-01-01 00:00:00
abstract：:Ubiquitin (Ub) carboxy terminal hydrolase (UCH)-L1 and UCH-L3 are two of the deubiquitinating enzymes expressed in the brain. Both gad mice, which lack UCH-L1 expression and Uchl3 knockout mice exhibit neurodegeneration, although at distinct areas. These phenotypes indicate the importance of UCH-L1 and UCH-L3 in the r...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2008.12.013
更新日期：2009-05-01 00:00:00
abstract：:Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with th...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2015.07.016
更新日期：2015-11-01 00:00:00
abstract：:Fatty acids play a critical role in brain function but their specific role in the pathophysiology of Parkinson disease (PD) and levodopa-induced motor complications is still unknown. From a therapeutic standpoint, it is important to determine the relation between brain fatty acids and PD because the brain fatty acid c...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2005.12.002
更新日期：2006-04-01 00:00:00
abstract：:In chicks submitted to light stimulation, the synthesis of gangliosides of the retina ganglion cell increases with respect to chicks maintained in the dark. In an attempt to elucidate if the activation of glycosyltransferases participates in the establishment of these light-dark differences detected in vivo, we examin...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(96)00128-3
更新日期：1997-07-01 00:00:00
abstract：:Insulin receptors from rat brain regions were studied for insulin binding and receptor associated kinase activity, in alloxan induced short-term and long-term diabetes, and insulin induced hypoglycemia. Insulin receptor activity was assessed by [125I]insulin binding, and basal as well as insulin stimulated kinase acti...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(92)90027-o
更新日期：1992-06-01 00:00:00
abstract：:The aim of the present study was to investigate, whether dopamine D1 and/or D2 receptors are able to interfere with the ATP-induced increase of the intracellular Ca2+ concentration ([Ca2+]i) in cultured striatal neurons identified by their morphological characteristics and their [Ca2+]i transients in response to a hig...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2007.06.013
更新日期：2008-01-01 00:00:00
abstract：:The effect of subcutaneous injections of saline (0.9% NaCl, 10-40 ?l/g b. wt) to 5- and 20-day old rats on the concentrations of tyrosine (Tyr) and tryptophan (Trp) in the serum and the brain and on the levels of biogenic amines and their metabolites in the developing brain at 6 h p.i. is described. At day 5 the conce...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(85)90071-3
更新日期：1985-01-01 00:00:00
abstract：:Ischemic neuronal injury is associated with several life- and vision-threatening diseases. Neuroprotection is essential in the treatment of these diseases. Here, we identified and characterized a novel peptide, FK18, from basic fibroblast growth factor (bFGF). We further assessed the neuroprotective effects of this pe...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2017.02.015
更新日期：2017-09-01 00:00:00
abstract：:Carotenoids play a pivotal role in prevention of many degenerative diseases mediated by oxidative stress including neurodegenerative diseases like Alzheimer's Disease (AD). The involvement of retinoids in physiology, AD pathology and their therapeutic role in vitro and in vivo has been extensively studied. This review...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2011.04.004
更新日期：2011-10-01 00:00:00
abstract：:Five glutamate transporter genes have been identified; two of these (EAAT3 and EAAT4) are expressed in neurons and are predominantly confined to the membranes of cell bodies and dendrites. At an ultrastructural level, glutamate transporters have been shown to surround excitatory synapses in hippocampus and cerebellum ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2003.11.007
更新日期：2004-09-01 00:00:00
abstract：:Excitotoxicity induced by excessive glutamate has been implicated in many brain disorders. Xanthohumol is a natural product derived from hops (Humulus lupulus L.), which is reported to have glutamate release-inhibiting activity. However, it is unknown whether xanthohumol has protective effects against glutamate-induce...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2019.104629
更新日期：2020-02-01 00:00:00
abstract：:AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) excitotoxicity was examined in cultured neocortical neurons using the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to measure cell viability. Neurons were exposed to AMPA at different culture periods during development o...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(97)00130-7
更新日期：1998-05-01 00:00:00
abstract：:Transport activity of d-pipecolic acid and of l-pipecolic acid in mouse brain and peripheral tissues were tested, and the effect of immobilization stress was described, along with the method for preparative, enantiomeric resolution and purification of d,l-pipecolic acid using high performance liquid chromatography equ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(88)90057-5
更新日期：1988-01-01 00:00:00
abstract：:Aminoethylcysteine ketimine is a sulfur-containing cyclic compound produced by the enzymatic alpha-deamination of the parent aminoethylcysteine that has been detected in bovine brain and cerebellum. Aminoethylcysteine ketimine is known to dimerize spontaneously and easily lose one carboxyl group. This decarboxylated c...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(97)00094-6
更新日期：1998-04-01 00:00:00
abstract：:The effects of ?-amino-n-butyric acid (GABA), (+)bicuculline, isoguvacine and 3-(4-chlorophenyl)-4-aminobutyrate [(+/-)baclofen] on the K-induced release of [(3)H]acetylcholine (ACh) were studied in the superior cervical ganglia of the rat in vitro. GABA and isoguvacine inhibited [(3)H]ACh release and these inhibition...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(86)90193-2
更新日期：1986-01-01 00:00:00
abstract：:The binding kinetics of the specific dopamine D2 antagonist [3H]raclopride to dopamine D2 receptors in rat neostriatum were studied. The pseudo-first-order rate constants of [3H]raclopride binding with these membranes revealed a hyperbolic dependence upon the antagonist concentration, indicating that the reaction had ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(95)00123-9
更新日期：1996-05-01 00:00:00
abstract：:Intrauterine growth retardation induced by ligation of the uterine vessels in pregnant rats on the 5th day before delivery was associated with brain and body weights of hypotrophic offspring significantly lower than those of pair-aged control rats, even after 6 weeks of postnatal rearing under normal conditions. In vi...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(85)90121-4
更新日期：1985-01-01 00:00:00
abstract：:It was shown previously that pure oligodendrocytes release proteins when maintained in a chemically defined medium. Among these proteins, a 53 kDa glycoprotein was characterized as a component accessible from the external surface of these glial cells. Specific antibodies directed against this glycoprotein were obtaine...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(88)90101-5
更新日期：1988-01-01 00:00:00
abstract：:A possible modulatory role of kinases on voltage sensitive Na+ channels of presynaptic brain nerve endings was investigated by testing the effect of several kinase activators and inhibitors on the elevation of [Nai] induced by veratridine in mouse brain synaptosomes loaded with a selective Na+ indicator dye. Veratridi...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(97)00065-x
更新日期：1998-02-01 00:00:00
abstract：:Variants in the gene encoding the enzyme glutamic acid decarboxylase like 1 (GADL1) have been associated with response to lithium therapy. Both GADL1 and the related enzyme cysteine sulfinic acid decarboxylase (CSAD) have been proposed to be involved in the pyridoxal-5'-phosphate (PLP)-dependent biosynthesis of taurin...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2015.08.013
更新日期：2015-11-01 00:00:00
abstract：:Glutamate is an excitotoxin responsible for causing neuronal damage associated with mitochondria dysfunction. We have analyzed the relationship between the mitochondrial respiratory rate, the membrane potential (delta psi) and the activity of mitochondrial complexes in retinal cells in culture, used as neuronal models...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(99)00107-2
更新日期：2000-02-01 00:00:00
abstract：:A number of principles have long guided research into serotonin neurochemistry and some of them are presently reconsidered with a slightly different outlook. An increasing amount of experimental data does not always support these older axioms and as more empirical observations are made, some of these may require modif...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(86)90157-9
更新日期：1986-01-01 00:00:00
abstract：:There is a growing body of evidence on the role of nitric oxide (NO) in retinal physiology. Recently, interest has developed in the functional role of an alternative redox form of NO, namely nitroxyl (HNO/NO(-)), because it is formed by a number of diverse biochemical reactions. The aim of the present report was to co...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2007.04.015
更新日期：2007-11-01 00:00:00
abstract：:Specific binding of [(3)H]d- fenfluramine , an anorectic agent acting on serotonergic system, was characterized in rat total brain minus cerebellum. The binding was reversible, stereospecific and with high affinity (K(d) about 80 nM). The receptor density in total brain was about 32 pmol/g tissue. Subcellular distribu...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(88)90007-1
更新日期：1988-01-01 00:00:00
abstract：:Growing evidence suggests that α-lipoic acid (LA) has neuroprotective effects in various pathological conditions including brain ischemia and neurodegeneration. While anti-oxidative activity has been thought to play a central role in LA-mediated neuroprotection, the precise mechanism and the effect of LA enantiomers (...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2011.09.005
更新日期：2011-12-01 00:00:00
abstract：:Aquaporin-4 (AQP4) is a key molecule for maintaining water and ion homeostasis associated with neuronal activity in the central nervous system, but the roles of AQP4 in adult neurogenesis remain largely unexplored. Based on preliminary evidences over the past years, AQP4 appears to emerge as an important player regula...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2010.01.014
更新日期：2010-04-01 00:00:00
abstract：:Parkinson's disease (PD), a progressive neurodegenerative disorder, has long been associated with mitochondrial dysfunction in both sporadic and familial forms of the disease. Mitochondria are crucial for maintaining cellular homeostasis, and their dysfunction is detrimental to dopaminergic neurons. These neurons are ...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2019.104495
更新日期：2019-10-01 00:00:00
abstract：:Guanylate cyclase in the membrane fraction of rod outer segments (ROS-membrane) from the frog retina showed an extremely high activity but had no responsiveness to NaN(3) (+catalase), nitrosoguanidine or superoxide dismutase. These compounds, however, markedly activated the enzyme in a soluble fraction from the retina...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(82)90006-7
更新日期：1982-01-01 00:00:00
abstract：:Antibodies to electrolectin, a lectin endogenous to embryonic skeletal muscle, have been used to study the distribution of lectin during myogenesis in L(6) cells by using immunohistofluorescence microscopy. Evidence for both surface and cytoplasmic forms of lectin is presented. Cytoplasmic lectin does not appear to be...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(80)90041-8
更新日期：1980-01-01 00:00:00
