Journal ArticleDOI
NMDA-dependent superoxide production and neurotoxicity
TLDR
It is reported that O·- 2 is produced upon NMDA receptor stimulation in cultured cerebellar granule cells and the nitrone DMPO (5,5-dimethyl pyrroline 1-oxide), used as a spin trap, is more efficient than the nitric oxide synthase inhibitor, L-N G -nitroarginine, in reducing NMDA-induced neuronal death in these cultures.Abstract:
NEURONAL injury resulting from acute brain insults and some neurodegenerative diseases implicates N-methyl-D-aspartate (NMDA) glutamate receptors1–4. The fact that antioxidants reduce some types of brain damage suggests that oxygen radicals may have a role5–7. It has been shown that mutations in Cu/Zn-superoxide dismutase (SOD), an enzyme catalysing superoxide (O·-2) detoxification in the cell, are linked to a familial form of amyotrophic lateral sclerosis (ALS)4. Here we report that O·-2 is produced upon NMDA receptor stimulation in cultured cerebellar granule cells. Electron paramagnetic resonance was used to assess O·-2 production that was due in part to the release of arachidonic acid. Activation of kainic acid receptors, or voltage-sensitive Ca2+ channels, did not produce detectable O·-2. We also find that the nitrone DMPO (5,5-dimethyl pyrroline 1-oxide), used as a spin trap, is more efficient than the nitric oxide synthase inhibitor, L-NG-nitroarginine, in reducing NMDA-induced neuronal death in these cultures.read more
Citations
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Journal ArticleDOI
Oxidants, oxidative stress and the biology of ageing.
Toren Finkel,Nikki J. Holbrook +1 more
TL;DR: Evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span is reviewed.
Journal ArticleDOI
Oxidative stress, glutamate, and neurodegenerative disorders
TL;DR: Two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain.
Journal ArticleDOI
Ischemic Cell Death in Brain Neurons
TL;DR: A major unifying thread of the review is a consideration of how the changes occurring during and after ischemia conspire to produce damaging levels of free radicals and peroxynitrite to activate calpain and other Ca(2+)-driven processes that are damaging, and to initiate the apoptotic process.
Journal ArticleDOI
Excitatory amino acids as a final common pathway for neurologic disorders.
TL;DR: In many neurologic disorders, injury to neurons may be caused at least in part by overstimulation of receptors for excitatory amino acids, including glutamate and aspartate.
Journal ArticleDOI
Dilated Cardiomyopathy and Neonatal Lethality in Mutant Mice Lacking Manganese Superoxide Dismutase
Yibing Li,Ting-Ting Huang,Elaine J. Carlson,Simon Melov,Philip C. Ursell,Jean L. Olson,Linda Noble,Midori P. Yoshimura,Christoph N. Berger,Christoph N. Berger,Pak H. Chan,Douglas C. Wallace,Charles J. Epstein +12 more
TL;DR: Cytochemical analysis revealed a severe reduction in succinate dehydrogenase and aconitase activities in the heart and, to a lesser extent, in other organs, which indicates that MnSOD is required for normal biological function of tissues by maintaining the integrity of mitochondrial enzymes susceptible to direct inactivation by superoxide.
References
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Journal ArticleDOI
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
Journal ArticleDOI
Glutamate, nitric oxide and cell-cell signalling in the nervous system
TL;DR: In this paper, it was shown that NO is produced enzymatically in postsynaptic structures in response to activation of excitatory amino acid receptors and diffuses out to act on neighbouring cellular elements, probably presynaptic nerve endings and astrocyte processes.
Journal ArticleDOI
Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures.
TL;DR: It is established that NO mediates the neurotoxicity of glutamate and Hemoglobin, which complexes NO, prevents neurotoxic effects of both N-methyl-D-aspartate and sodium nitroprusside.
Journal ArticleDOI
Excitatory amino acid neurotoxicity and neurodegenerative disease
Brian S. Meldrum,John Garthwaite +1 more
TL;DR: In vivo and in vitro studies of the cytotoxicity of amino acids are reviewed and the contribution of such toxicity to acute and chronic neurodegenerative disorders is summarized.