Editors' ChoiceNitric Oxide

When NO Means No to a Neuron

Science's STKE  20 Aug 2002:
Vol. 2002, Issue 146, pp. tw310
DOI: 10.1126/stke.2002.146.tw310

Nitric oxide can modify cysteine residues on proteins and produce an S-nitrosylated derivative (see the review by Lane et al.). Gu et al. report that such a modification of matrix metalloproteinase-9 (MMP-9) activates the enzyme. MMP-9 nitrosylation and activation were observed in rodent brain tissue upon stroke, and treatment of cultured neurons with NO-activated MMP-9 caused apoptosis. This activation pathway may contribute to neuronal cell death that is associated with the extracellular matrix disruption observed in cerebral ischemia and neurodegenerative diseases.

P. Lane, G. Hao, S. S. Gross, S-Nitrosylation is emerging as a specific and fundamental posttranslational protein modification: Head-to-head comparison with O-phosphorylation. Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/sigtrans;2001/86/re1 [Abstract] [Full Text]

Z. Gu, M. Kaul, B. Yan, S. J. Kridel, J. Cui, A. Strongin, J. W. Smith, R. C. Liddington, S. A. Lipton, S-Nitrosylation of matrix metalloproteinases: Signaling pathway to neuronal cell death, Science 297, 1186-1190 (2002). [Abstract] [Full Text]