Gliotoxic actions of excitatory amino acids

Bridges, Richard J.; Hatalski, Carolyn G.; Shim, Sung N.; Cummings, Brian J.; Vijayan, Vijaya K.; Kundi, A.; Cotman, Carl W.

doi:10.1016/0028-3908(92)90128-c

Cited by 46 publications

(26 citation statements)

References 33 publications

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“…Increased intracellular levels of calcium stimulate several catabolic enzymes such as phospholipases, proteases and endonucleases and can thereby lead to cell death [90,93,94]. The concept of excitotoxicity has been implicated in the pathogenesis of acute (hypoglycaemia and ischaemia) and chronic neuronal degeneration (Huntington's disease, amyotrophic lateral sclerosis and Alzheimer's disease) [90,93,95].…”

Section: Sulphur-containing Excitatory Amino Acidsmentioning

confidence: 99%

“…First, sulphur-containing amino acids are capable of releasing the excitatory amino acids aspartate and glutamate [96,97] and to inhibit the reuptake of these neurotransmitters in neuronal and glial plasma membranes [98][99][100][101][102] which is considered to be the most important mechanism to control levels of excitatory amino acids in the synaptic cleft and hence avoid toxicity. Moreover, damage to astrocytes induced by MTX [103,104] or sulphur-containing amino acids [95] may contribute to an increased excitatory transmission since astrocytes manage the enzymatic inactivation of glutamate. Elevated excitotoxic levels of glutamate could further damage astrocytes leading to an increased vulnerability of neurones and glia cells [95].…”

Section: Sulphur-containing Excitatory Amino Acidsmentioning

confidence: 99%

“…Moreover, damage to astrocytes induced by MTX [103,104] or sulphur-containing amino acids [95] may contribute to an increased excitatory transmission since astrocytes manage the enzymatic inactivation of glutamate. Elevated excitotoxic levels of glutamate could further damage astrocytes leading to an increased vulnerability of neurones and glia cells [95].…”

Section: Sulphur-containing Excitatory Amino Acidsmentioning

confidence: 99%

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Biochemical and Clinical Aspects of Methotrexate Neurotoxicity

Vezmar¹,

Becker²,

et al. 2003

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Acute, subacute and chronic neurotoxicity have been observed after the administration of high-dose and/or intrathecal methotrexate (MTX). Acute toxicity is usually transient without permanent damage. Subacute and chronic toxicity are associated with changes in the brain and/or the spinal cord which may be progressive and even lead to coma and death in severe cases. It is believed that MTX can induce direct toxic effects to the CNS by damaging the neuronal tissue. Moreover, MTX interferes with the metabolic pathways of folates, excitatory amino acids, homocysteine, S-adenosylmethionine/S-adenosylhomocysteine, adenosine and biopterins, inducing biochemical alterations which have been associated with neurotoxic symptoms. It has been suggested that acute toxicity is partly mediated by adenosine, whereas homocysteine, S-adenosylmethionine/S-adenosylhomocysteine, excitatory amino acids and biopterins may play an important role in the development of subacute and chronic toxicity. A better understanding of the pathogenesis of MTX neurotoxicity would offer the possibility of developing new therapeutic strategies for its treatment or prevention.

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Section: Sulphur-containing Excitatory Amino Acidsmentioning

confidence: 99%

Section: Sulphur-containing Excitatory Amino Acidsmentioning

confidence: 99%

Section: Sulphur-containing Excitatory Amino Acidsmentioning

confidence: 99%

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Biochemical and Clinical Aspects of Methotrexate Neurotoxicity

Vezmar¹,

Becker²,

et al. 2003

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“…L-αAminoadipate (L-αAA), L-β−N-oxalylamino-L-alanine (L-BOAA) and L-homocysteate are substrates and/ or inhibitors of the x c -cystine-glutamate exchanger (Kato et al, 1993;Patel et al, 2004;Warren et al, 2004) and belong to a group of glutamate analogues that have been termed 'gliotoxins' (Bridges et al, 1992). We have previously used 13 C NMR spectroscopy to show that incubation of C6 glioma cells with a sub-toxic concentration of gliotoxins causes metabolic disruption and a decrease in glutathione production (Brennan et al, 2004).…”

Section: Introductory Statementmentioning

confidence: 99%

Glutathione depletion causes a JNK and p38MAPK-mediated increase in expression of cystathionine-γ-lyase and upregulation of the transsulfuration pathway in C6 glioma cells

Kandil

Brennan

McBean

2010

Neurochemistry International

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“…Excess tHcy can be metabolized to sulfur-containing excitatory amino acid neurotransmitters, including homocysteic acid and cysteine sulfine acid, as well as the related compounds tHcy sulfonic acid and cysteic acid [25,26]. These endogenous agonists of N-methyl-D-aspartate receptors are likely important in the genesis of seizures [27] and, further, may cause neuronal injury or death through excessive glutamate receptor activation, called excitotoxicity [28][29][30]. Excitatory amino acids and excitotoxicity have been implicated as a final common pathway for a wide range of chronic neurodegenerative disorders, as well as a number of acute neurologic processes, including cerebral ischemia and stroke [30].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Vitamin B12, Folate, and Vitamin B6 Supplements in Elderly People with Normal Serum Vitamin B12 Concentrations

Henning

Tepel

Riezler³

et al. 2001

Gerontology

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Background: In the elderly, deficiencies of folate, cobalamin (vitamin B₁₂) and pyridoxal phosphate (vitamin B₆) are common. The metabolites homocysteine, methylmalonic acid, 2-methylcitric acid and cystathionine have been reported to be sensitive markers of these vitamin deficiencies. Objective: The long-term (269 days) effect of an intramuscular vitamin supplement containing 1 mg vitamin B₁₂, 1.1 mg folate, and 5 mg vitamin B₆ on serum concentrations of homocysteine (tHcy), methylmalonic acid (MMA), 2-methylcitric acid (2-MCA), and cystathionine (Cysta) was studied in 49 elderly subjects with normal levels of vitamin B₁₂. Methods: Vitamin supplement was administered 8 times over a 21-day period, metabolite concentrations were measured until day 269 (e.g. 248 days after the end of vitamin supplementation). Results: From day 0 to 21, the serum levels of the 3 vitamins increased significantly, after cessation of supplementation the levels returned to baseline within the follow-up period. The MMA, 2-MCA and tHcy levels decreased during the treatment period significantly and did not reach baseline values within the 248-day period. Cysta levels did not differ significantly from baseline, either during or after treatment. Conclusion: MMA and 2-MCA levels rather reflect the availability of vitamins, especially cobalamin, than the actual serum levels. Since deficiencies of folate, cobalamin and pyridoxal phosphate in the elderly may cause hyerhomocysteinemia and hence may have unfavorable effects on mental performance, determination of MMA and 2-MCA levels in elderly patients with mental disturbances may be a cost-effective measure to improve or maintain mental performance.

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Gliotoxic actions of excitatory amino acids

Cited by 46 publications

References 33 publications

Biochemical and Clinical Aspects of Methotrexate Neurotoxicity

Biochemical and Clinical Aspects of Methotrexate Neurotoxicity

Glutathione depletion causes a JNK and p38MAPK-mediated increase in expression of cystathionine-γ-lyase and upregulation of the transsulfuration pathway in C6 glioma cells

Long-Term Effects of Vitamin B<sub>12</sub>, Folate, and Vitamin B<sub>6</sub> Supplements in Elderly People with Normal Serum Vitamin B<sub>12</sub> Concentrations

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