Reporters to monitor cellular MMP12 activity

Amanda Cobos-Correa, Marcus A. Mall, Carsten Schultz

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Macrophage elastase, also called MMP12, belongs to a family of proteolytic enzymes whose best known physiological function is the remodeling of the extracellular matrix. Under certain pathological conditions, including inflammation, chronic overexpression of MMP12 has been observed and its elevated proteolytic activity has been suggested to be the cause of pulmonary emphysema. However, it was until recently impossible to monitor the activity of MMP12 under disease conditions, mainly due to a lack of detection methods. Recent development of new reporters for monitoring MMP12 activity in living cells, such as LaRee1, provided novel insights into the pathobiology of MMP12 in pulmonary inflammation. In the future, these reporters might contribute to improved diagnosis and in finding better treatments for chronic inflammatory lung diseases and emphysema. Our approach for visualizing MMP12 activity is based on peptidic, membrane-targeted FRET (Foerster Resonance Energy Transfer) reporters. Here we describe a set of new reporters containing different fluorophore pairs as well as modifications in the membrane-targeting lipid moiety. We studied the influence of these modifications on reporter performance and the reporter mobility on live cell membranes by FRAP (fluorescence recovery after photobleaching). Finally, we generated several new fluorescently labeled MMP inhibitors based on the peptidic reporter structures as prototypes for future tools to inhibit and monitor MMP activity at the same time.

Original languageEnglish (US)
Title of host publicationReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II
DOIs
StatePublished - May 10 2010
EventReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II - San Francisco, CA, United States
Duration: Jan 25 2010Jan 27 2010

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume7576
ISSN (Print)1605-7422

Other

OtherReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II
CountryUnited States
CitySan Francisco, CA
Period1/25/101/27/10

Keywords

  • Activity
  • FRAP
  • FRET
  • Fluorescence
  • Inflammation
  • Lipidation
  • MMP12

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Atomic and Molecular Physics, and Optics
  • Radiology Nuclear Medicine and imaging

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  • Cite this

    Cobos-Correa, A., Mall, M. A., & Schultz, C. (2010). Reporters to monitor cellular MMP12 activity. In Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II [757605] (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 7576). https://doi.org/10.1117/12.842113