Nitric Oxide Activates Killer Enzymes

Researchers have found that nitric oxide, found in the body and as an air pollutant, can activate metalloproteinases (MMPs), enzymes that have been implicated in the pathogenesis of neurodegenerative diseases and stroke. The research was reported in the August 16, 2002, issue of Science.

Investigators from the Burnham Institute (La Jolla, CA, USA) employed mass spectrometry to identify the active derivative of an MMP, both in vitro and in vivo, as a stable sulfinic or sulfonic acid, whose formation was triggered by S-nitrosylation. The activated MMP was found to have a proteolytic effect on the outside of nerve cells, eventually leading to death of the cells.

"The MMP enzymes act outside of the nerve cell rather than inside,” said Dr. Stuart Lipton, director of the Center for Neuroscience and Aging at The Burnham Institute. "Previously, the best-characterized enzyme pathways that killed nerve cells were found inside nerve cells rather than outside. The fact that nitric oxide could activate these enzymes was not previously recognized.”

"Now that we know about this new pathway to nerve cell death that occurs outside of the cells, we can design drugs to interrupt it, and that is where the work will go in the future, said Dr. Lipton. "The work gives us a new way to think about preventing excessive activity of MMP enzymes, and as such it could lead to new therapies for stroke and several neurodegenerative diseases.”



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The Burnham Institute