kainic acid-induced excitotoxicity: Topics by WorldWideScience.org

Evidence for proteolytic cleavage of brevican by the ADAMTSs in the dentate gyrus after excitotoxic lesion of the mouse entorhinal cortex

A study was made of the actions of the excitant neurotoxin, kainic acid, on the uptake and the release of D-(2,3-3H)aspartate (D-ASP) in slices of guinea pig cerebral neocortex and striatum. The slices took up D-ASP, reaching concentrations of the amino acid in the tissue which were 14-23 times that in the medium. Subsequently, electrical stimulation of the slices evoked a Ca2+-dependent release of a portion of the D-ASP. Kainic acid (10(-5)-10(-3) M) produced a dose-dependent inhibition of D-ASP uptake. The electrically evoked release of D-ASP was increased 1.6-2.0 fold by 10(-5) and 10(-4)M kainic acid. The kainate-enlarged release was Ca2+-dependent. Dihydrokainic acid, an analogue of kainic acid with little excitatory or toxic action, did not increase D-ASP release but depressed D-ASP uptake. Attempts were made to block the action of kainic acid with baclofen and pentobarbital, ...

1983-06-01

Endothelin-1 Is Increased in Cerebrospinal Fluid and Associated with Unfavorable Outcomes in Children after Severe Traumatic Brain Injury

BackgroundBrevican is a member of the lectican family of aggregating extracellular matrix (ECM) proteoglycans that bear chondroitin sulfate (CS) chains. It is highly expressed in...Full Text Available

Characterization of neurotoxic effects of NMDA and the novel neuroprotection by phytopolyphenols in mice.

AbstractSevere pediatric traumatic brain injury (TBI) is associated with unfavorable outcomes secondary to injury from activation of the inflammatory cascade, the release of excitotoxic...Full Text Available

2010-10-01

Recombinant human activated protein C ameliorates oleic acid-induced lung injury in awake sheep

Excitotoxicity plays a major role in various neurological disorders. In this study, we explored the behavioral and neurotoxic effects of intraventricular NMDA administration in mice. After NMDA injection, acute seizures were followed by impairments in locomotor activity, motor performance on a rotarod, and climbing ability. Mice killed 1 day after NMDA administration showed increased synaptosomal reactive oxygen species ROS production and calcium concentration and decreased mitochondrial membrane potential, mitochondrial reductase activities, and neuronal membrane Na+, K+ -ATPase and mg2+ -ATPase activities. One and 3 days after excitotoxic injury, Golgi stains showed that dendritic length and spine density were significantly decreased in neurons of the hippocampal dentate gyrus. Some mice received honokiol, tea polyphenol plus memantine, and honokiol plus memantine prior to NMDA treatment; the occurrence of generalized seizures was attenuated, ...

2010-08-01

Differential recognition of viral RNA by RIG-I

IntroductionAcute lung injury (ALI) may arise both after sepsis and non-septic inflammatory conditions and is often associated with the release of fatty acids, including oleic acid...Full Text Available

2008-01-01

Targeting the kynurenine pathway as a potential strategy to prevent and treat Alzheimer's disease

Retinoic acid inducible gene I (RIG-I) is a pattern recognition receptor (PRR) responsible for detection of nucleic acids from pathogens in the cytoplasm of infected cells and induction of type I interferon...Full Text Available

2011-03-01

British Library Electronic Table of Contents (United Kingdom)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only...

2011-01-01

Selective downregulation of retinoic acid-inducible gene I within the intestinal epithelial compartment in crohn's disease

British Library Electronic Table of Contents (United Kingdom)

AbstractBackground: A defective innate immune response may contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Employing a global gene expression analysis, this study was aimed at identifying specifically regulated genes within the epithelial compartment in inflammatory bowel disease (IBD). Methods: The epithelial fraction of human ileal mucosa samples from surgical specimens was obtained by laser microdissection. Gene expression was examined by global expression profiling (n = 18, Affymetrix), quantitative reverse-transcription polymerase chain reaction (RT-PCR) (n = 35), immunoblot analysis (n = 9), and immunohistochemistry (n = 25). Results: Global expression profiling revealed a pronounced downregulation of the retinoic acid-inducible gene I (RIG-I) with...

2011-01-01

The noradrenergic system in cultured aggregates of fetal rat brain cells: morphology of the aggregates and pharmacological indices of noradrenergic neurons

Conjugation is essential for the anticholestatic effect of NorUrsodeoxycholic acid in taurolithocholic acid induced cholestasis in rat liver

Spherical aggregates formed rapidly in culture by re-aggregation of trypsin-dissociated brain cells from the 17-day-old fetal rat. Over about 10 days an initially random distribution of cells evolved into a 3-layered arrangement; cells with characteristics of neurons were found largely in the intermediate layer. The survival of neuronal and glial cell types was evaluated histologically and verified by electron microscopy, which revealed synaptic and myelin structures that rapidly increased in number after 18 days in culture. Levels of norepinephrine (NE) and dopamine (DA) reached peaks of 9.5 and 4.4 ng/mg protein, respectively, at culture day 21. Uptake of ["3H]NE paralleled these amine levels and was blocked by desipramine or pretreatment with either reserpine or 6-OH-DA. Autoradiographs of aggregates labeled with ["3H]NE showed a high density of silver grains over cells, apparently neurons, with branching processes traced for 120 #mu#m. Previously accumulated ["3H]NE was released ...

British Library Electronic Table of Contents (United Kingdom)

Abstract NorUDCA (24 norursodeoxycholic acid), the C23 homolog of ursodeoxycholic acid (UDCA), showed remarkable therapeutic effects in cholestatic Mdr2 (Abcb4) (multidrug resistance protein 2/ATP binding cassette b4) knockout mice with sclerosing/fibrosing cholangitis. In contrast to UDCA, norUDCA is inefficiently conjugated in human and rodent liver, and conjugation has been discussed as a key step for the anticholestatic action of UDCA in cholestasis. We compared the choleretic, anticholestatic, and antiapoptotic properties of unconjugated and taurine conjugated UDCA (C24) and norUDCA (C23) in isolated perfused rat liver (IPRL) and in natrium/taurocholate cotransporting polypeptide (Ntcp) transfected human hepatoma (HepG2) cells. Taurolithocholic acid (TLCA) was used to induce a predomi...

2010-01-01

5,8,11,14-Eicosatetraynoic acid-induced destruction of mitochondria in human prostate cells (PC-3).

Simple Methods for Determining Relative Stereochemistry of Kainoid Amino Acids by (1)H NMR Chemical Shifts.

Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA.

1992-01-01

Involvement of a glutamergic mechanism in gamma-dendrotoxin-induced hippocampal neuronal cell loss in the rat.

The kainoid amino acids are biologically important compounds because they show remarkable neuroexcitatory and excitotoxic activities. For exhibiting potent activity, the stereochemical relationship of the substituents on the pyrrolidine ring is crucial. We found simple methods for determining the relative stereochemistry of these compounds on the basis of the (1)H NMR chemical shifts of H-2 and H-4 in D(2)O solution. The signals of H-2 appear at fields higher than 4.2 ppm when the compounds have 2,3-trans stereochemistry whereas, in the 2,3-cis compounds, they appear lower than 4.2 ppm, irrespective of the C-4 substituent. This criterion holds when the solution is in the range of pD 3-8. Moreover, when an epimeric pair at C-2 is available and the spectra are recorded at the same or nearly equal pD, the H-2 chemical shift of the 2,3-trans isomer is higher than that of the corresponding 2,3-cis isomer. Similarly, the relative stereochemistry between C-3 and C-4 can ...

1996-07-12

Supplementation of pyruvate prevents palmitate-induced impairment of glucose uptake in C2 myotubes.

The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticeps, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats pretreated with CGP040116, a N-methyl-D-aspartate (NMDA) receptor antagonist, and in rats bearing a monolateral surgical lesion of the Schaffer collaterals whose terminals originate from CA3 pyramids and release glutamate in the CA1 hippocampal area. Administration of 35 pmol gamma-dendrotoxin elicited in all of the treated animals (n=8) bilateral EEG discharges and damage to the hippocampal formation. Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1, CA3 and CA4 pyramidal cell layers. The lowest dose (0.35 pmol; n=4) of the toxin used did not affect EEG activity and failed to cause significant hippocampal cell loss whereas the 3.5 pmol (n=6) dose caused EEG seizures and hippocampal cell loss limited to the ...

2004-03-01

Hyaluronic acid production by irradiated human synovial fibroblasts

Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and ?-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the intracellular pyruvate level. These results suggest ...

2011-07-23

Effect of drought and abscisic acid application on the osmotic adjustment of four wheat cultivars

Radioactive particles as well as x irradiation from an external source has been used in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In order to clarify effects of ionizing irradiation on synovial cells, radioactive gold ("1"9"8Au) and yttrium ("9"0Y) were added to fibroblast cultures derived from human synovial membranes. Other cultures were irradiated by a Picker x-ray machine. Fibroblast growth and hyaluronic acid production were measured. Radioactive gold and yttrium particles induced a significant increase of hyaluronic acid synthesis rate (pg/cell/day) and inhibited fibroblast growth. Fibroblasts continued to overproduce hyaluronic acid and to show growth inhibition 3 weeks after irradiation with radioactive gold. Hydrocortisone inhibited hyaluronic acid overproduction induced by radioactive gold. Overproduction of hyaluronic acid induced by the x-ray machine was inhibited by hydrocortisone, ...

1977-01-01

Chiral salicyloxazolines as auxiliaries for the asymmetric synthesis of ruthenium polypyridyl complexes.

The accumulation of osmolytes in leaf tissues and the abscisic acid-induced stomatal closure are well-recognized mechanisms associated with drought tolerance in crop plants. We determine the response in terms of osmotic potential and the contents of leaf proline, glycine betaine and soluble sugar at booting and grain filling stages of four wheat (Triticum aestivum L.) cultivars to drought and exogenously applied abscisic acid (ABA) in a pot study. Leaf sample were collected 3, 6 and 9 days after drought induction and at 48 and 72 h of re-watering (recovery). Marked decreases in osmotic potential associated with the accumulation of proline, glycine betaine and soluble sugars occurred under conditions of drought stress Accession 011320 was most sensitive to drought and showed the largest decrease in osmotic potential and least accumulation of proline, sugar and glycine betaine The inhibitory effects of drought stress were ameliorated by exogenous application of ABA. ...

2010-02-01

Bip overexpression, but not CHOP inhibition, attenuates fatty-acid-induced endoplasmic reticulum stress and apoptosis in HepG2 liver cells

Chiral auxiliaries are promising emerging tools for the asymmetric synthesis of octahedral metal complexes. We recently introduced chiral salicyloxazolines as coordinating bidentate chiral ligands which provide excellent control over the metal-centered configuration in the course of ligand substitution reactions and can be removed afterward in an acid-induced fashion under complete retention of configuration (J. Am. Chem. Soc. 2009, 131, 9602-9603). Here reported is our detailed investigation of this sequence of reactions, affording virtually enantiopure ruthenium polypyridyl complexes. The control of the metal-centered chirality by the coordinated chiral salicyloxazolinate ligand was evaluated as a function of reaction conditions, the employed bidentate 2,2'-bipyridine and 1,10-phenanthroline ligands, and the substituent at the asymmetric 5-position of the oxazoline heterocycle. Most striking was the strong influence of the reaction solvent, with aprotic solvents ...

2010-09-01

British Library Electronic Table of Contents (United Kingdom)

Aims: In this study we investigated whether attenuation of endoplasmic reticulum stress (ER stress) could protect HepG2 cells from free fatty acid (FFA)-induced apoptosis. Main methods: Human liver cell line HepG2 cells were exposed to Sodium Palmitate (Pa) or Sodium Oleate (Ol). Apoptosis and ER stress of HepG2 cells were analyzed with flow cytometry, real-time RT-PCR and Western Blotting. An expression plasmid encoding for the ER chaperone immunoglobulin heavy chain-binding protein (Bip) was transfected into HepG2 cells to attenuate ER stress. Small interfering RNA siCHOP was used to knockdown the expression of C/EBP Homologous Protein (CHOP) in HepG2. Key findings: Pa led to cytotoxicity and apoptosis in HepG2 cells in a dose-dependent pattern and also induced ER stress indicated by inc...

2010-01-01

The Effects of Surface Chemistry on the Properties of Proteins Confined in Nano-porous Materials

Antiperoxidative and antiinflammatory effect of Sida cordifolia Linn. on quinolinic acid induced neurotoxicity.

The entrapment of proteins using the sol-gel route provides a means to retain its native properties and artificially reproduce the molecular crowding and confinement experienced by proteins in the cell allowing investigation of the physico-chemical and structural properties of biomolecules at the biotic/abiotic interface. The biomolecules are spatially separated and 'caged' in the gel structure but solutes can freely permeate the matrix. Thus, properties such as the folding of ensembles of individual molecules can be examined in the absence of aggregation effects that can occur in solution studies. Green fluorescent protein from Aequorea coerulescens was used as a model protein to examine the unfolding/re-folding properties of protein in silica gels. The recombinant protein was isolated and purified from Escherichia coli extracts by cell lysis, three-phase partitioning, dialysis, and anion exchange chromatography. The purity of the protein was greater than 90% as ...

2007-09-01

A criterion to determine whether cis-4-hydroxyproline is produced in animal tissues

Sida cordifolia is a plant belonging to the Malvaceae family used in many ayurvedic preparations. This study aimed at assessing the effects of ethanolic extract of Sida cordifolia root on quinolinic acid (QUIN) induced neurotoxicity and to compare its effect with the standard drug deprenyl in rat brain. Rats were divided into six groups: (1) control group (2) QUIN (55 microg/100 g bwt/day) (3) 50% ethanolic plant extract treated group (50 mg/100 g bwt/day) (4) Deprenyl (100 microg/100 g bwt/day) (5) QUIN (55 microg/100 g bwt/day) + 50% ethanolic plant extract treated group (50 mg/100 g bwt/day) (6) QUIN (55 microg/100 g bwt/day) + Deprenyl (100 microg/100 g bwt/day). At the end of the experimental period a status of lipid peroxidation products, protein peroxidation product, activities of the scavenging enzymes and the activities of the inflammatory markers were analyzed. Results revealed that the lipid peroxidation products decreased and the activities of the scavenging enzymes ...

2010-05-25

1 2

A criterion to determine whether cis-4-hydroxyproline is produced in animal tissues

Hydrolyzates of tissues that had been labeled with (14C)proline often contain significant amounts of cis-4-hydroxy(14C)proline. Since animal cells do not contain an enzyme which can effect formation of cis-4-hydroxyproline, there are only two possible explanations for its presence. Either it is formed during acid hydrolysis of trans-4-hydroxyproline (which is synthesized by cells and is a common constituent of connective tissues), or it is produced by a nonenzymatic mechanism such as attack by oxygen radicals. It is important to resolve this issue because if a nonenzymatic mechanism is active in connective tissues, then it will be necessary to reevaluate currently accepted ideas about production of hydroxyproline. This communication describes a method for distinguishing between the two alternate explanations. Tissues or cells are labeled with (14C)proline, and then a known amount of trans-4-hydroxy(3H)proline is added to each sample before hydrolysis; the relative amounts of (14C)- and ...

1984-03-01