Biomaterial Database

Neuroprotective versus neurodestructive effects of NO-related species. 1998

S A Lipton, and Y B Choi, and N J Sucher, and H S Chen

CNS Research Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. slipton@rics.bwh.harvard.edu

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.

UI	MeSH Term	Description	Entries
D007473	Ion Channels	Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.	Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009498	Neurotoxins	Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.	Alpha-Neurotoxin,Excitatory Neurotoxin,Excitotoxins,Myotoxin,Myotoxins,Neurotoxin,Alpha-Neurotoxins,Excitatory Neurotoxins,Excitotoxin,Alpha Neurotoxin,Alpha Neurotoxins,Neurotoxin, Excitatory,Neurotoxins, Excitatory
D009566	Nitrates	Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical.	Nitrate
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D002490	Central Nervous System	The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.	Cerebrospinal Axis,Axi, Cerebrospinal,Axis, Cerebrospinal,Central Nervous Systems,Cerebrospinal Axi,Nervous System, Central,Nervous Systems, Central,Systems, Central Nervous
D005996	Nitroglycerin	A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.	Glyceryl Trinitrate,Anginine,Dynamite,Gilustenon,Nitrangin,Nitro-Bid,Nitro-Dur,Nitrocard,Nitroderm,Nitroderm TTS,Nitroglyn,Nitrol,Nitrolan,Nitrong,Nitrospan,Nitrostat,Perlinganit,Susadrin,Sustac,Sustak,Sustonit,Transderm Nitro,Tridil,Trinitrin,Trinitrolong,Nitro Bid,Nitro Dur,NitroBid,NitroDur,Trinitrate, Glyceryl
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013481	Superoxides	Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.	Superoxide Radical,Superoxide,Superoxide Anion