Alteration in the glial cell metabolism of glutamate by kainate and N-methyl-D-aspartate

McBean, Gethin J.; Doorty, Kevina B.; Tipton, Keith F.; Kollegger, H.

doi:10.1016/0041-0101(94)00187-d

Cited by 19 publications

(11 citation statements)

References 31 publications

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“…Nitration of glutamate transporters by peroxynitrite inhibits their ability to transport glutamate from the synaptic cleft to the neurons where it is then metabolized to non-toxic glutamine by glutamine synthase [85]. Nitration of the active site tyrosine residue (Tyr-160) on glutamine synthase by peroxynitrite destroys its enzymatic activity [82][83][84]. As a consequence, excitotoxic and neurotoxic glutamate accumulates in the synaptic cleft where it is not metabolized, and within neurons, thereby leading to neurotoxicity.…”

Section: Peroxynitrite and Oxidative/nitrative Stressmentioning

confidence: 98%

“…For example, glutamate transporters and glutamine synthase play a central role in regulating the homoeostasis of extracellular glutamate and its metabolic fate. These proteins are also nitrated by peroxynitrite [80][81][82][83][84]. Nitration of glutamate transporters by peroxynitrite inhibits their ability to transport glutamate from the synaptic cleft to the neurons where it is then metabolized to non-toxic glutamine by glutamine synthase [85].…”

Section: Peroxynitrite and Oxidative/nitrative Stressmentioning

confidence: 98%

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Superoxide, peroxynitrite and oxidative/nitrative stress in inflammation

Salvemini

Doyle

Cuzzocrea

2006

Biochemical Society Transactions

148

115

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A considerable body of evidence suggests that formation of potent reactive oxygen species and resulting oxidative/nitrative stress play a major role in acute and chronic inflammation and pain. Much of the knowledge in this field has been gathered by the use of pharmacological and genetic approaches. In this mini review, we will evaluate recent advances made towards understanding the roles of reactive oxygen species in inflammation, focusing in particular on superoxide and peroxynitrite. Given the limited space to cover this broad topic, here we will refer the reader to comprehensive review articles whenever possible.

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Section: Peroxynitrite and Oxidative/nitrative Stressmentioning

confidence: 98%

Section: Peroxynitrite and Oxidative/nitrative Stressmentioning

confidence: 98%

Superoxide, peroxynitrite and oxidative/nitrative stress in inflammation

Salvemini

Doyle

Cuzzocrea

2006

Biochemical Society Transactions

148

115

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“…The generation of Á NO by either pharmacological means [31][32][33][34][35] or the applications of cytokines [36,37], results in the inhibition of glutamine synthetase activity in vivo. This inhibition is prevented by blockade of cellular nitric oxide synthase activity [31][32][33][35][36][37], except in the case of benzodiazepine-treated astrocytes [34]. Interestingly, the addition of nitric oxide synthetase inhibitors alone increases glutamine synthetase activity and suggests the activity of this enzyme is controlled tonically by Á NO [32,35].…”

Section: Nitration Of Glutamine Synthetasementioning

confidence: 99%

Critical Evaluation of the Changes in Glutamine Synthetase Activity in Models of Cerebral Stroke

2015

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The following article addresses some seemingly paradoxical observations concerning cerebral glutamine synthetase in ischemia-reperfusion injury. In the brain, this enzyme is predominantly found in astrocytes and catalyzes part of the glutamine-glutamate cycle. Glutamine synthetase is also thought to be especially sensitive to inactivation by the oxygen- and nitrogen-centered radicals generated during strokes. Despite this apparent sensitivity, glutamine synthetase specific activity is elevated in the affected tissues during reperfusion. Given the central role of the glutamine-glutamate cycle in the brain, we sought to resolve these conflicting observations with the view of providing an alternative perspective for therapeutic intervention in stroke.

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“…NO reversibly inhibits GS activity suggesting that a covalent modification such as nitrosylation or nitration causes its inhibition (Kosenko et al, 2003). Nitric oxide synthase (NOS) inhibition results in an increase in GS activity in cultured astrocytes and in the rat brain (Minana et al, 1997; Kosenko et al, 2003; Rose and Felipo, 2005) and reportedly protected GS from NMDA-induced inactivation in brain slices (McBean et al, 1995). The generation of ONOO − from the reaction of NO with O 2 · − may further nitrate protein tyrosine residues (Beckman and Koppenol, 1996) and has been shown to inactivate mammalian GS in vitro (Gorg et al, 2007).…”

Section: 1 Seizure-induced Oxidative Damage To Cellular Macromolecumentioning

confidence: 99%

Mitochondria, oxidative stress, and temporal lobe epilepsy

2010

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Mitochondrial oxidative stress and dysfunction are contributing factors to various neurological disorders. Recently, there has been increasing evidence supporting the association between mitochondrial oxidative stress and epilepsy. Although certain inherited epilepsies are associated with mitochondrial dysfunction, little is known about its role in acquired epilepsies such as temporal lobe epilepsy. Mitochondrial oxidative stress and dysfunction are emerging as key factors that not only result from seizures, but may also contribute to epileptogenesis. The occurrence of epilepsy increases with age, and mitochondrial oxidative stress is a leading mechanism of aging and age-related degenerative disease, suggesting a further involvement of mitochondrial dysfunction in seizure generation. Mitochondria have critical cellular functions that effect neuronal excitability including production of adenosine triphosphate (ATP), fatty acid oxidation, control of apoptosis and necrosis, regulation of amino acid cycling, neurotransmitter biosynthesis, and regulation of cytosolic Ca2+ homeostasis. Mitochondria are the primary site of reactive oxygen species (ROS) production making them uniquely vulnerable to oxidative stress and damage which can further affect cellular macromolecule function, the ability of the electron transport chain to produce ATP, antioxidant defenses, mitochondrial DNA stability, and synaptic glutamate homeostasis. Oxidative damage to one or more of these cellular targets may affect neuronal excitability and increase seizure susceptibility. The specific targeting of mitochondrial oxidative stress, dysfunction, and bioenergetics with pharmacological and non-pharmacological treatments may be a novel avenue for attenuating epileptogenesis and seizure initiation.

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Alteration in the glial cell metabolism of glutamate by kainate and N-methyl-D-aspartate

Cited by 19 publications

References 31 publications

Superoxide, peroxynitrite and oxidative/nitrative stress in inflammation

Superoxide, peroxynitrite and oxidative/nitrative stress in inflammation

Critical Evaluation of the Changes in Glutamine Synthetase Activity in Models of Cerebral Stroke

Mitochondria, oxidative stress, and temporal lobe epilepsy

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