Neuroprotective versus neurodestructive effects of NO-related species.
Nitric oxide (NO.) can lead to damaging or protective actions in the central nervous system. Here we consider the chemistry of the NO group and its redox-related species that can lead to these exactly opposite ends. In the neurodestructive mode, NO. reacts with superoxide anion (02.-) to form peroxynitrite (ONOO-), which leads to neuronal injury. In contrast, the reaction of the NO group with cysteine sulfhydryls on the NMDA receptor leads to a decrease in receptor/channel activity. avoidance of excessive Ca2+ entry, and thus neuroprotection. Site-directed mutagenesis of recombinant NMDA receptor subunits has recently increased our knowledge of such redox modulation by NO. Transfer of the NO group to cysteine sulfhydryls on the NMDA receptor or other proteins, known as S-nitrosylation, is becoming recognized as a ubiquitous regulatory reaction, skin to phosphorylation, and represents a form of redox modulation in diverse tissues including the brain.
CNS Research Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. slipton@rics.bwh.harvard.edu
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Lipton
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Choi
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Sucher
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Chen
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D015536:Down-Regulation; D007473:Ion Channels / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D010084:Oxidation-Reduction; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000502:physiology; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism
D007473:Ion Channels; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009566:Nitrates; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; D005996:Nitroglycerin