Affiliations: CNS Research Institute, Brigham and Women’s Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Note: [] Send correspondence to: Stuart A. Lipton, M.D., Ph.D., CNS Research Institute, Brigham and Women’s Hospital, 221 Longwood Avenue – LMRC First Floor, Boston, MA 02115, USA. Tel.: 617 278 0363; Fax: 617 264 5277; E‐mail: slipton@ rics.bwh.harvard.edu.
Note: [] Present address: Department of Biology, Hong Kong University of Science and Technology, Hong Kong, China.
Abstract: Nitric oxide (NO\mathbin{\hbox{\tenbsy\char"01}}) 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\mathbin{\hbox{\tenbsy\char"01}} reacts with superoxide anion (O_{2}\mathbin{\hbox{\tenbsy\char"01}}^-) 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 Ca^{2+} 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, akin to phosphorylation, and represents a form of redox modulation in diverse tissues including the brain.
Journal: Biofactors, vol. 8, no. 1-2, pp. 33-40, 1998
