Journal of Neurochemistry
1471-4159
0022-3042
Anh Quốc
Cơ quản chủ quản: Wiley-Blackwell Publishing Ltd , WILEY
Lĩnh vực:
BiochemistryCellular and Molecular Neuroscience
Phân tích ảnh hưởng
Thông tin về tạp chí
Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
Các bài báo tiêu biểu
EFFECTS OF ALUMINUM SALTS ON CULTURED NEUROBLASTOMA CELLS Abstract Experimental induction of neurofibrillary tangles was demonstrated several years ago in the central nervous system of rabbits injected with aluminum salts. In the current studies, neuroblastoma cells, capable of morphologic and biochemical differentiation in monolayer culture, have been exposed to medium containing aluminum phosphate; such treatment resulted in an abundant accumulation of 100 Å neurofilaments after 6 days of continous exposure to the aluminum salt. While growth rates and incorporation of radioactive thymidine in treated cells remained similar to controls, total cellular protein, and incorporation of radioactive leucine were significantly increased. Paradoxically, when the protein content of aluminum‐treated cultures was maximal, these cultures contained about 20 per cent less ribosomal RNA per cell than in control cultures. In addition, activity of an important neuronal protein, i.e. acetylcholinesterase, was depressed in treated cultures to a level below control values. Both temporal and morphologic similarities between treated neuroblastoma cultures and animals injected with aluminum salts suggest that the observed changes in macromolecular synthesis in cell culture are relevant to in vivo studies.
Tập 22 Số 5 - Trang 751-758 - 1974
Rapid production of diacylglycerols enriched in arachidonate and stearate during early brain ischemia
Tập 25 Số 6 - Trang 919-920 - 1975
SNARE Proteins‐Why So Many, Why So Few? Abstract: Both trafficking and secretion critically depend on accurate and specific membrane recognition and fusion. A key step in these processes is the assembly of a complex consisting of a small number of proteins, i.e., the exocytic core complex. In nerve terminals, this set consists of VAMP and synaptotagmin, which reside at membranes of synaptic vesicles, and syntaxin and SNAP‐25 at the plasma membrane. In this survey, different secretory systems that depend on the exocytic core proteins are considered. The possibility that specificity in membrane recognition and fusion is achieved by the numerous variants of proteins of the exocytic core is discussed. Variability of the core complex proteins is determined by the complexity of gene families, isoform‐specific localization, and posttranslational modifications. Basic biochemical properties depend on specific isoforms, and the possible protein‐protein interactions are determined, in turn, by the compatibility of different isoforms. A correlation between specific variants and distinct biochemical or cellular properties is shown. The outcome of this survey is that heterogeneity in secretion may be dictated by the large number of possible combinations of variants of only a few proteins.
Tập 69 Số 5 - Trang 1781-1792 - 1997
Histochemical Study of Aldehyde Dehydrogenase in the Rat CNS A quantitative histochemical method was developed to determine aldehyde dehydrogenase (EC 1.2.1.3; ALDH) activity in the CNS. The distribution of ALDH activity in all rat brain and spinal cord regions is described. Among the CNS neuron structures, high enzyme activity was found in receptor and effector neurons, whereas low activity was noted in perikarya of the majority of intermediate neurons, including all aminergic neurons. A positive correlation was demonstrated between the distribution of ALDH activity among rat CNS microregions (our own data) and the density of dopaminergic terminals, dopamine content, and monoamine oxidase activity (literature data) among the same microregions. They may reflect a spatial linkage between ALDH and the predicted sites of natural aldehyde production. Lower enzyme activity was found in phylogenetically younger brain structures. It may explain the differential resistance of CNS structures to ethanol (acetaldehyde). Among the barrier CNS structures, moderate ALDH activity was found in capillaries and surrounding astrocytes and high activity was noted in ependimocytes covering the brain cavities and those of the vascular plexus. This provides realization of the function of ALDH as a brain metabolic barrier for aldehydes.
Tập 56 Số 1 - Trang 1-11 - 1991
ENZYMES CATALYSING ETHANOL METABOLISM IN NEURAL AND SOMATIC TISSUES OF THE RAT Abstract— The enzymes catalysing ethanol metabolism, alcohol dehydrogenase (EC 1.l.1.1) and aldehyde dehydrogenase (EC 1.2.1.3), were assayed in a variety of neural and somatic tissues of the rat, the human counterparts of which are known to be vulnerable to excessive ethanol. The activity of alcohol dehydrogenase was assayed by the coupled oxidation of ethanol and reduction of lactaldehyde, a method which we have recently found to be sufficiently sensitive and specific to measure the relatively low levels of activity in whole brain. Detectable activities of these enzymes were found in peripheral nerve, skeletal muscle, retina, optic nerve and various regions of brain, as well as in a variety of non‐neural tissues. The levels of the enzymic activities in all tissues were markedly lower than those of liver, but probably sufficient to perform a local function in the metabolism of ethanol or other endogenous substrates. The activity of alcohol dehydrogenase in the various tissues, like that of liver, was confined to the cytosol and exhibited kinetic properties and responses to inhibitors almost identical to those of the liver enzyme. We consider the results to be consistent with the hypothesis that the pathological effects of alcohol may be related, at least in part, to local mechanisms for the metabolism of alcohol.
Tập 19 Số 2 - Trang 273-282 - 1972
Zinc inhibition of cellular energy production: implications for mitochondria and neurodegeneration Abstract An increasing body of evidence suggests that high intracellular free zinc promotes neuronal death by inhibiting cellular energy production. A number of targets have been postulated, including complexes of the mitochondrial electron transport chain, components of the tricarboxylic acid cycle, and enzymes of glycolysis. Consequences of cellular zinc overload may include increased cellular reactive oxygen species (ROS) production, loss of mitochondrial membrane potential, and reduced cellular ATP levels. Additionally, zinc toxicity might involve zinc uptake by mitochondria and zinc induction of mitochondrial permeability transition. The present review discusses these processes with special emphasis on their potential involvement in brain injury.
Tập 85 Số 3 - Trang 563-570 - 2003
4‐Hydroxynonenal Induces Oxidative Stress and Death of Cultured Spinal Cord Neurons Abstract: Primary spinal cord trauma can trigger a cascade of secondary processes leading to delayed and amplified injury to spinal cord neurons. Release of fatty acids, in particular arachidonic acid, from cell membranes is believed to contribute significantly to these events. Mechanisms of fatty acid‐induced injury to spinal cord neurons may include lipid peroxidation. One of the major biologically active products of arachidonic acid peroxidation is 4‐hydroxynonenal (HNE). The levels of HNE‐protein conjugates in cultured spinal cord neurons increased in a dose‐dependent manner after a 24‐h exposure to arachidonic acid. To study cellular effects of HNE, spinal cord neurons were treated with different doses of HNE, and cellular oxidative stress, intracellular calcium, and cell viability were determined. A 3‐h exposure to 10 μM HNE caused ∼80% increase in oxidative stress and 30% elevation of intracellular calcium. Exposure of spinal cord neurons to HNE caused a dramatic loss of cellular viability, indicated by a dose‐dependent decrease in MTS [3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H ‐tetrazolium, inner salt] conversion. The cytotoxic effect of HNE was diminished by pretreating neurons with ebselen or N ‐acetylcysteine. These data support the hypothesis that formation of HNE may be responsible, at least in part, for the cytotoxic effects of membrane‐released arachidonic acid to spinal cord neurons.
Tập 74 Số 6 - Trang 2278-2287 - 2000
Stimulation of [<sup>3</sup>H]GABA and β‐[<sup>3</sup>H]Alanine Release from Rat Brain Slices by <i>cis</i>‐4‐Aminocrotonic Acid Abstract: cis ‐4‐Aminocrotonic acid (CACA; 100 µM ), an analogue of GABA in a folded conformation, stimulated the passive release of [3 H]GABA from slices of rat cerebellum, cerebral cortex, retina, and spinal cord and of β‐[3 H]alanine from slices of cerebellum and spinal cord without influencing potassium‐evoked release. In contrast, CACA (100 µM ) did not stimulate the passive release of [3 H]taurine from slices of cerebellum and spinal cord or of d ‐[3 H]aspartate from slices of cerebellum and did not influence potassium‐evoked release of [3 H]taurine from the cerebellum and spinal cord and d ‐[3 H]aspartate from the cerebellum. These results suggest that the effects of CACA on GABA and β‐alanine release are due to CACA acting as a substrate for a β‐alanine‐sensitive GABA transport system, consistent with CACA inhibiting the uptake of β‐[3 H]alanine into slices of rat cerebellum and cerebral cortex. The observed K i for CACA against β‐[3 H]alanine uptake in the cerebellum was 750 ± 60 µM . CACA appears to be 10‐fold weaker as a substrate for the transporter system than as an agonist for the GABAc receptor. The effects of CACA on GABA and β‐alanine release provide indirect evidence for a GABA transporter in cerebellum, cerebral cortex, retina, and spinal cord that transports GABA, β‐alanine, CACA, and nipecotic acid that has a similar pharmacological profile to that of the GABA transporter, GAT‐3, cloned from rat CNS. The structural similarities of GABA, β‐alanine, CACA, and nipecotic acid are demonstrated by computer‐aided molecular modeling, providing information on the possible conformations of these substances being transported by a common carrier protein.
Tập 68 Số 2 - Trang 786-794 - 1997
Inhibiting α1‐adrenergic receptor signaling pathway ameliorates <scp>AD</scp>‐type pathologies and behavioral deficits in <scp>APPswe</scp>/<scp>PS1</scp> mouse model Abstract The role of α1 adrenergic receptors (α1‐ARs) signaling pathway in the pathogenesis of Alzheimer's disease (AD) has rarely been investigated. Clarifying the pathophysiological functions of α1‐ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic targets of AD. This study included 2 arms of in vivo investigations: 1) 6‐month‐old female APPswe/PS1 mice were intravenously treated with AAV‐PHP.eB‐shRNA (α1‐ARs)‐GFP or AAV‐PHP.eB‐GFP for 3 months. 2) 3‐month‐old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or an equal volume of saline for 6 months. SH‐SY5Y cell lines bearing human amyloid precursor protein were treated with terazosin or saline for investigating possible mechanisms. α1‐ARs knockdown mice exhibited improved behavioral performances in comparison with control mice. α1‐ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aβ species, compact and total Aβ plaques, than control mice. α1‐ARs inhibitor terazosin substantially reduced Aβ deposition, attenuated downstream pathologies including tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction et al., and rescued behavioral deficits in APPswe/PS1 mice. In vitro investigation demonstrated that α1‐ARs inhibition down‐regulated BACE1 expression, and promoted ser9 phosphorylation of GSK‐3β, thus reducing Aβ production. This study indicates that inhibition of α1‐ARs signaling pathway might represent a promising therapeutic strategy for AD.image
Tập 161 Số 3 - Trang 293-307 - 2022
Brain‐specific potential guanine nucleotide exchange factor for Arf, synArfGEF (Po), is localized to postsynaptic density Abstract We cloned from a rat brain cDNA library a novel cDNA and named it a potential synaptic guanine nucleotide exchange factor (GEF) for Arf (synArfGEF (Po)) (GenBank Accession no. AB057643 ) based on its domain structure and localization. The cloned gene was 7410 bases long with a 3585‐bp coding sequence encoding a protein of 1194 amino acids. The deduced protein contained a coiled‐coil structure in the N‐terminal portion followed by Sec7 and Plekstrin homology (PH) domains. Thus, the protein was a member of the Sec7 family of proteins, GEFs. Conservation of the ADP‐ribosylation factor (Arf)‐binding sequence suggested that the protein was a GEF for Arf. The gene was expressed specifically in the brain, where it exhibited region‐specific expression. The protein was highly enriched in the postsynaptic density (PSD) fraction prepared from the rat forebrain. Uniquely, the protein interacted with PSD‐95, SAP97 and Homer/Vesl 1/PSD‐Zip45 via its C‐terminal PDZ‐binding motif and co‐localized with these proteins in cultured cortical neurons. These results supported its localization in the PSD. The postsynaptic localization was also supported by immunohistochemical examination of the rat brain. The mRNA for the synArfGEF was also localized to dendrites, as well as somas, of neuronal cells. Thus, both the mRNA and the protein were localized in the postsynaptic compartments. These results suggest a postsynaptic role of synArfGEF in the brain.
Tập 89 Số 6 - Trang 1347-1357 - 2004