Glutamate induces H2O2 synthesis in nonsynaptic brain mitochondria

Lobysheva, N. V.; Selin, A.A.; Vangeli, I. M.; Byvshev, I. M.; Yaguzhinsky, L. S.; Nartsissov, Yaroslav R.

doi:10.1016/j.freeradbiomed.2013.07.030

Cited by 12 publications

(25 citation statements)

References 25 publications

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“…Hama-Tomioka et al (39) also noted the link between increased O 2 − production and activation of NOX2 (NADPH oxidase subunit) by NMDA receptors. Also, Ca 2+ overload due to NMDA receptor activation induce increased H 2 O 2 production in complex I, III and II (41). The lack of a vasodilatory effect of NO in our study could be the consequence of conversion of NO and O 2 − to peroxynitrite, which is one of free radicals with most potent deleterious effect and could mediate the adverse effects of NMDA stimulation by glycine and glutamate (42,43).…”

Section: Discussionmentioning

confidence: 54%

“…Their results suggested that NAC may prevent the glutamate-induced apoptosis of cultured rat cardiomyocytes and, in this manner, potentially prevent reduction of myocardial function. Experiments with isolated brain mitochondria revealed a significant increase in H 2 O 2 production induced by glutamate, which were prevented by MK-801 (NMDA receptor antagonist) (41). The proposed underlying mechanism for increased NO 2 − levels, which mirror NO production, is activation of NOS and NADPH oxidase (38).…”

Section: Discussionmentioning

confidence: 99%

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The effects of glycine, glutamate and their combination on cardiodynamics, coronary flow and oxidative stress in isolated rat hearts

Srejović¹,

Jakovljević²

2015

Curr Res Cardiol

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ObJeCTIVeS: To examine the effects of glycine, glutamate and their combination on cardiac function, coronary flow and oxidative stress in isolated rat hearts, and to examine the effects of potential activation of N-methyl-Daspartate (NMDA) receptors in isolated rat hearts. MeThODS: The hearts of male Wistar albino rats were excised and perfused according to the Langendorff technique, and cardiodynamic parameters (maximum rate of pressure development in the left ventricle [dp/dt max]; minimum rate of pressure development in the left ventricle [dp/dt min], systolic left ventricular pressure, diastolic left ventricular pressure, heart rate) and coronary flow were determined during the subsequent administration of glycine, glutamate and their combination. Oxidative stress biomarkers, including thiobarbituric acid-reactive substances, nitrites (NO 2 −), superoxide anion radical (O 2 −) and hydrogen peroxide (H 2 O 2), were each determined spectrophotometrically in coronary venous effluent. ReSulTS: Treatment with glycine and glutamate alone did not cause a statistically significant change in any of the observed parameters; however, their combined administration induced significant decreases in dp/dt max, dp/dt min, heart rate and coronary flow compared with the control conditions. Treatment with glycine and glutamate together induced significant increases in NO 2 − , O 2 − and H 2 O 2 levels. After the washout period, all parameters that had changed (cardiodynamic parameters, coronary flow and levels oxidative stress biomarkers) returned to values that were not significantly different from controls. CONCluSIONS: The results of the present study indicate that NMDA receptors likely have important roles in the function of the heart and coronary circulation. In addition, these results are suggestive of a damaging effect of NMDA receptor overstimulation in heart functioning, potentially mediated by oxidative stress.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

The effects of glycine, glutamate and their combination on cardiodynamics, coronary flow and oxidative stress in isolated rat hearts

Srejović¹,

Jakovljević²

2015

Curr Res Cardiol

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“…Experimental evidence indicates that changes in the concentration of three of the discriminant metabolites we identified—namely lactate, creatine, and taurine—can be associated with an increased oxidative stress [Jang & Kim, ; Lobysheva et al, ; Ribeiro, Silva, Rodrigues, Naia, & Rego, ; Won et al, ]. By being described that these molecules can have a protective effect by decreasing the formation of reactive oxygen species or the production of superoxide anion, their decrease in our patients can support the presence of an oxidative stress condition in autistic individuals.…”

Section: Discussionmentioning

confidence: 57%

The urinary ¹H‐NMR metabolomics profile of an italian autistic children population and their unaffected siblings

et al. 2017

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Autism spectrum disorders (ASD) make a dishomogeneous group of psychiatric diseases having either genetic and environmental components, including changes of the microbiota. The rate of diagnosis, based on a series of psychological tests and observed behavior, dramatically increased in the past few decades. Currently, no biological markers are available and the pathogenesis is not defined. The purpose of this study was to evaluate the potential use of H-NMR metabolomics to analyze the global biochemical signature of ASD patients (n = 21) and controls (n = 21), these being siblings of autistic patients. A multivariate model has been used to extrapolate the variables of importance. The discriminating urinary metabolites were identified; in particular, significantly increased levels of hippurate, glycine, creatine, tryptophan, and d-threitol and decreased concentrations of glutamate, creatinine, lactate, valine, betaine, and taurine were observed in ASD patients. Based on the identified discriminant metabolites, the attention was focused on two possible mechanisms that could be involved in ASD: oxidative stress conditions and gut microflora modifications. In conclusion, nuclear magnetic resonance-based metabolomics analysis of the urine seems to have the potential for the identification of a metabolic fingerprint of ASD phenotypes and appears to be suitable for further investigation of the disease mechanisms. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1058-1066. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

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“…Oxidative stress lead to protein dysfunction, DNA damage and lipid peroxidation, resulting in cell death in a manner that is dependent on the excessive production of ROS ( 18 ). A recent study revealed that 1-50 mM glutamate affected H 2 O 2 synthesis by brain mitochondria, and this effect was associated with complex II, a source of superoxide formation in mitochondria, and is dependent on the mitochondrial potential ( 19 ). Ha et al ( 20 ) revealed that, following prolonged exposure to glutamate, extracellular H 2 O 2 accumulated in a time- and concentration-dependent manner in HT22 cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of valproic acid on oxidative stress parameters of glutamate‑induced excitotoxicity in SH‑SY5Y cells

Oğuz

Acet

2020

Exp Ther Med

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Glutamate-induced excitotoxicity has been reported to be involved in the pathophysiology of neurodegenerative disorders. It has been proposed that valproic acid (VPA), which is used in epileptic and bipolar disorders, may be protective against excitotoxic insult. The aim of the present study was to investigate the effects of VPA against the glutamate excitotoxicity in the SH-SY5Y human neuroblastoma cell line and determine its anti-oxidant capacity by measuring oxidative and anti-oxidant biochemical parameters. SH-SY5Y human neuroblastoma cells were pre-treated with 1, 5 or 10 mM VPA prior to exposure to 15 mM glutamate. The MTT assay was performed to determine cell viability. To detect oxidative insult in glutamate toxicity and the potential anti-oxidant effect of VPA, the cell catalase (CAT), superoxide dismutase (SOD), malondialdehyde and hydrogen peroxide (H 2 O 2 ) activity was determined. A progressive decline in cell viability was observed with increasing glutamate concentrations (1-50 mM). Treatment with 1 mM VPA was revealed to be effective in increasing the viability of cells exposed to glutamate for 24 h. Oxidative damage, including an increase in H 2 O 2 and MDA, was observed in SH-SY5Y cells treated with glutamate and was reduced by pre-treatment with VPA. CAT activity was decreased following glutamate exposure, but VPA did not prevent this decrease. SOD activity was increased by treatment with VPA alone and was not affected by glutamate exposure. Overall, the present results confirmed the critical role of oxidative stress in glutamate-induced excitotoxicity. They also suggested that VPA may exert an anti-oxidant effect against glutamate-induced excitotoxicity by decreasing oxidative parameters, including H 2 O 2 and MDA, but only had a slight effect on CAT and SOD activity, which have an anti-oxidant capacity.

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Glutamate induces H2O2 synthesis in nonsynaptic brain mitochondria

Cited by 12 publications

References 25 publications

The effects of glycine, glutamate and their combination on cardiodynamics, coronary flow and oxidative stress in isolated rat hearts

The effects of glycine, glutamate and their combination on cardiodynamics, coronary flow and oxidative stress in isolated rat hearts

The urinary ¹H‐NMR metabolomics profile of an italian autistic children population and their unaffected siblings

Effect of valproic acid on oxidative stress parameters of glutamate‑induced excitotoxicity in SH‑SY5Y cells

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Glutamate induces H2O2 synthesis in nonsynaptic brain mitochondria

Cited by 12 publications

References 25 publications

The effects of glycine, glutamate and their combination on cardiodynamics, coronary flow and oxidative stress in isolated rat hearts

The effects of glycine, glutamate and their combination on cardiodynamics, coronary flow and oxidative stress in isolated rat hearts

The urinary 1H‐NMR metabolomics profile of an italian autistic children population and their unaffected siblings

Effect of valproic acid on oxidative stress parameters of glutamate‑induced excitotoxicity in SH‑SY5Y cells

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The urinary ¹H‐NMR metabolomics profile of an italian autistic children population and their unaffected siblings