Redox-control of matrix metalloproteinase-1: a critical link between free radicals, matrix remodeling and degenerative disease

Respir Physiol Neurobiol. 2010 Dec 31;174(3):299-306. doi: 10.1016/j.resp.2010.08.019. Epub 2010 Sep 8.

Abstract

Many degenerative disease processes associated with aging result from enhanced extracellular matrix (ECM) breakdown. Concomitant with aberrant matrix destruction are alterations in levels of reactive oxygen species (ROS) generating and detoxification systems. ROS function as second messengers due to their ability to react with wide range of biomolecules resulting in modification of an array of signaling networks. ROS can activate upstream kinases (MKK) responsible for MAPK activation and restrict the activity of their inhibitory phosphatases. Here we focus on the redox-sensitive signaling components that control the expression of MMP-1, which is largely responsible for maintaining ECM homeostasis. Numerous disease processes are associated with shifts in steady state ROS levels that influence overall ECM degradation. This review highlights the redox-sensitive regulatory signals that control the expression of the primary initiating protease MMP-1 and provides strong rational for the use of antioxidant based therapies for treatment of degenerative disorders associated with aberrant matrix destruction.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Free Radicals / metabolism*
  • Humans
  • MAP Kinase Signaling System
  • Matrix Metalloproteinase 1 / metabolism*
  • Neurodegenerative Diseases / enzymology*
  • Neurodegenerative Diseases / physiopathology*
  • Oxidation-Reduction*
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism

Substances

  • Free Radicals
  • Reactive Oxygen Species
  • Matrix Metalloproteinase 1