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1
Agonist-activated Ca2plus and Co2plus influx through divalent cation-permeable kainate receptors
100%
Salinska E. , Lazarewicz J. W.
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nr 5
2
Characterization and modulation of calcium ionophores activated by NMDA and non-MNDA-receptor stimulation
100%
Salinska E. , Lazarewicz J. W.
Acta Neurobiologiae Experimentalis
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1992
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tom 52
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nr 3
3
Excitotoxic neuronal injury in chronic homocysteine neurotoxicity studied in vitro: The role of MNDA and group I metabotropic glutamate receptors
100%
Zieminska E. , Lazarewicz J. W.
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2006
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tom 66
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nr 4
EN
Elevated homocysteine is a risk factor in cardiovascular diseases and neurodegeneration. Among the putative mechanisms of homocysteineevoked neurotoxicity, disturbances in methylation processes and NMDA receptor-mediated excitotoxicity have been suggested. Our previous studies demonstrated that group I metabotropic glutamate receptors along with NMDA receptors participate in acute homocysteine-induced neuronal damage. In this study, using propidium iodide staining, we tested whether the same mechanism may mediate chronic homocysteine neurotoxicity. Our results confirmed that the application of D,L-homocysteine in micromolar concentrations for 3 days induces neurodegeneration in primary cultures of cerebellar granule neurons. Uncompetitive NMDA receptor antagonist MK801, and mGlu1 or mGlu5 receptor antagonists (LY367385 and MPEP, respectively), given alone provided very limited neuroprotection. However, simultaneous application of the NMDA receptor antagonists MK-801, memantine or amantadine and MPEP almost completely prevented chronic homocysteine neurotoxicity. These findings suggest a novel therapeutic strategy to combat neurodegeneration induced by hyperhomocysteinemia comprising a combination of antagonists of group I metabotropic glutamate receptors and NMDA receptors.
4
Role of calcium in glutamate-mediated toxicity ; mechanisms of calcium fluxes in rabbit hippocampus in vivo investigated with microdialysis
100%
Lazarewicz J. W. , Salinska E.
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tom 53
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nr 1
5
Differential expression of NMDA-evoked 45 Ca release in rat hippocampal regions in vivo
100%
Lazarewicz J. W. , Rybkowski W.
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nr 2
6
Strychnine antagonizes GABA-evoked 36 CI- uptake in membrane vesicles from rat and rabbit cerebral cortex
100%
Puka M. , Lazarewicz J. W.
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tom 53
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nr 4
7
Tetrabromobisphenol A-induced oxidative stress in primary cultures of rat cerebellar granule cells:triggering role of CA2plus imbalance
80%
Zieminska E. , Lenart J. , Lazarewicz J. W.
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tom 75
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nr Supl.
EN
BACKGROUND AND AIMS: Brominated flame retardant tetrabromobisphenol A (TBBPA) contaminates the environment and displays cytotoxic potential. The mechanism of its cytotoxicity in neurons encompasses interference with NMDA and ryanodine receptors (NMDARs and RyRs) resulting in increase in intracellular Ca2+ concentration (Ca2+i), and induction of oxidative stress, which may be primary, or secondary to rises in Ca2+i. The aim of this study was to assess the role of excitotoxicity and Ca2+ imbalance in TBBPA-evoked oxidative stress and cytotoxicity in neurons. METHODS: Using the primary cultures of rat cerebellar granule cells (CGC) we evaluated oxidative stress induced by an acute challenge with 10 or 25 µM TBBPA by measuring reactive oxygen species (ROS) production, intracellular glutathione (GSH) level, SOD-1 and SOD-2 level, catalase activity, and the level of Zn2+ in CGC. Zn2+ and Ca2+i were measured fluoromertically, moreover TBBPA toxicity 24 h after the exposure was evaluated using propidium iodide staining. The pharmacological tools included NMDARs antagonist MK-801, ryanodine with bastadin 12 inhibiting RyRs, and various free radical scavengers. RESULTS: TBBPA induced concentration-dependent decrease in CGC viability, increase in Ca2+i and Zn2+ level, in ROS production, decrease in GSH level, catalase activity and SOD-2 level. Co-application of NMDARs and RyRs inhibitors which completely prevented increase in Ca2+i, resulted in a significant, but not complete cytoprotection, and only partially reduced the oxidative stress in the CGC. Also administration of ROS scavengers provided only partial cytoprotection and reduction of oxidative stress. CONCLUSIONS: We conclude that the production of free radicals resulting secondarily from TBBPA-evoked excitotoxicity and increases in Ca2+ level together with oxidative stress possibly induced primarily by TBBPA, both participate in TBBPA cytotoxicity in cultured neurons. Supported by the NCN grant 2012/05/B/NZ7/03225.
8
Role of group 1 metabotropic glutamate receptors in homocysteine neurotoxicity
80%
Zieminska E. , Stafiej A. , Kozlowska H. , Lazarewicz J. W.
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tom 65
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nr 3
9
Tetrabromobisphenol A directly interferes with activity of NMDA isolated cortical membranes
80%
Diamandakis D. , Zieminska E. , Salinska E. , Lazarewicz J. W.
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tom 75
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nr Supl.
EN
BACKGROUND AND AIMS: The results of early studies suggested a role of glutamate receptors in the mechanism of increases in intracellular Ca2+ concentration ([Ca2+]i ) and cytotoxicity induced by the brominated flame retardant, tetrabromobisphenol-A (TBBPA). Although now interest has focused mainly on TBBPA-induced Ca2+ release from intracellular stores, here we revisited the former issue and tested the involvement of NMDA receptors (NMDARs) in Ca2+ imbalance in neurons induced by TBBPA. METHODS: These effects were examined in primary cultures of rat cerebellar granule cells (CGC), and then, using isolated cortical membranes we checked whether TBBPA directly interacts with the agonist and modulatory sites of the NMDAR complex. On the 7th day in vitro CGC were treated with TBBPA at low µM concentrations. 45Ca uptake was detected and changes in [Ca2+]i , and plasma membrane potential were measured using fluorescent probes fluo-3 and oxonol VI, respectively. Moreover effects of TBBPA on specific binding of [3 H]MK-801, [3 H]glutamate and [3 H]glycine to isolated fraction of the rat brain cortex membranes were studied. RESULTS: The results demonstrated that TBBPA concentrationdependently increased 45Ca uptake and [Ca2+]i in CGC, and the increase was partially inhibited by NMDARs antagonist, MK-801. This effect was additive to glutamate-induced Ca2+ transients. TBBPA increased oxonol VI fluorescence in CGC reflecting depolarization of the cultured neurons. The binding assays demonstrated potentiation by TBBPA binding of [ 3 H]MK-801 in the presence of NMDA and glycine, with maximum at 20 µM TBBPA, which was inhibited by spermidine and antagonists of the polyamines’ site; inhibition by TBBPA of [ 3 H]glutamate binding, and no significant effect on [3 H]glycine binding. CONCLUSIONS: TBBPA directly enhances the activity of NMDARs in neuronal membranes by interfering with their modulatory sites, and by inducing depolarization of neurons. Supported by the NCN grant 2012/05/B/NZ7/03225
10
Effects of NMDA antagonism on induced schemic tolerance in the gerbil hippocampus
80%
Lazarewicz J. W. , Gadamski R. , Danysz W.
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nr 3
11
Ligands of metabotropic glutamate receptors are neuroprotective in rat model of perinatal asphyxia
80%
Makarewicz D. , Wroblewski J. T. , Danysz W. , Lazarewicz J. W.
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tom 65
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nr 3
12
Prostacyclin reduces early ischemic changes in central nervous system
80%
Pluta R. , Salinska E. , Lazarewicz J. W.
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nr 4-5
13
NMDA-induced mitochondrial permeability transition in rabbit brain: in vivo and in vitro study
80%
Zieminska E. , Matyja E. , Ziembowicz A. , Lazarewicz J. W.
Acta Neurobiologiae Experimentalis
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1999
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tom 59
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nr 3
14
Pharmacological profiles of NMDA-induced eicosanoid release in rabbit hippocampus in vivo
80%
Zieminska E. , Salinska E. , Stafiej A. , Lazarewicz J. W.
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nr 5
15
Homocysteine neurotoxicity:involvement of calcium and mitochondrial alternations
80%
Zieminska E. , Kozlowska H. , Stafiej A. , Lazarewicz J. W.
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2006
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tom 66
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nr 4
16
NMDA - induced processing of beta-APP in hippocampus in vivo and in vitro
80%
Gordon-Krajcer W. , Salinska E. , Lazarewicz J. W.
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nr 5
17
Ryanodine receptors participate in the induction of mitochondrial permeability transition and excitotoxinc damage of cultured rat cerebellar granule cells
80%
Zieminska E. , Gordon-Krajcer W. , Matyja E. , Lazarewicz J. W.
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nr 3
18
Effect of methylnicotinamide on MMPs activity after neonatal cerebral hypoxia-ischemia
80%
Dragun P. , Makarewicz D. , Zalewska T. , Lazarewicz J. W.
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2006
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tom 66
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nr 4
19
Noradrenaline - and glutamate - induced taurine release from bulk isolated adult rat astrocytes
80%
Puka M. , Albrecht J. , Lazarewicz J. W.
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nr 1
20
Glycine enhances extracellular 45Ca2 response to NMDA application investigated with microdialysis of rabbit hippocampus in vivo
80%
Lazarewicz J. W. , Salinska E. , Puka M.
Acta Neurobiologiae Experimentalis
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1992
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tom 52
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nr 2
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