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S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death

Zezong Gu1, Marcus Kaul, Boxu Yan

  • 1Center for Neuroscience and Aging, Program in Cell Adhesion and Extracellular Matrix Biology, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Science (New York, N.Y.)
|August 17, 2002
PubMed

Insights

Matrix metalloproteinases (MMPs) activation, crucial in neurodegeneration and stroke, involves S-nitrosylation. This process activates MMP-9, leading to neuronal apoptosis via a novel extracellular proteolysis pathway.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Matrix metalloproteinases (MMPs) play a role in neurodegenerative diseases and stroke.
  • The precise mechanism of MMP activation in these conditions is not fully understood.

Purpose of the Study:

  • To elucidate the mechanism of MMP activation in the context of neurological disorders.
  • To investigate the role of S-nitrosylation in MMP activation and neuronal cell death.

Main Methods:

  • In vivo studies of cerebral ischemia.
  • In vitro experiments to assess MMP-9 activation.
  • Mass spectrometry for identifying MMP-9 derivatives.
  • Analysis of neuronal apoptosis.

Main Results:

  • MMP-9 was found to colocalize with neuronal nitric oxide synthase during cerebral ischemia.
  • S-nitrosylation was demonstrated to activate MMP-9 in vitro, inducing neuronal apoptosis.
  • Mass spectrometry identified a stable sulfinic or sulfonic acid derivative of MMP-9, formed via S-nitrosylation, in both in vitro and in vivo samples.

Conclusions:

  • S-nitrosylation is a key mechanism for activating MMPs, including MMP-9.
  • This activation pathway contributes to neuronal cell death in conditions like stroke.
  • Oxidation of S-nitrosylated MMPs leads to stable, pathologically active posttranslational modifications.

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