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
Volume7576
DOIs
StatePublished - 2010
Externally publishedYes
EventReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II - San Francisco, CA, United States
Duration: Jan 25 2010Jan 27 2010

Other

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

Fingerprint

Fluorescence Recovery After Photobleaching
Pulmonary Emphysema
Matrix Metalloproteinase Inhibitors
Pancreatic Elastase
Energy Transfer
Emphysema
Membrane Lipids
Matrix Metalloproteinases
Lung Diseases
Extracellular Matrix
Pneumonia
Peptide Hydrolases
Macrophages
Cell Membrane
Inflammation
Membranes
Photobleaching
emphysema
Pulmonary diseases
Fluorophores

Keywords

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

ASJC Scopus subject areas

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

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 (Vol. 7576). [757605] https://doi.org/10.1117/12.842113

Reporters to monitor cellular MMP12 activity. / Cobos-Correa, Amanda; Mall, Marcus A.; Schultz, Carsten.

Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II. Vol. 7576 2010. 757605.

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

Cobos-Correa, A, Mall, MA & Schultz, C 2010, Reporters to monitor cellular MMP12 activity. in Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II. vol. 7576, 757605, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II, San Francisco, CA, United States, 1/25/10. https://doi.org/10.1117/12.842113
Cobos-Correa A, Mall MA, Schultz C. Reporters to monitor cellular MMP12 activity. In Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II. Vol. 7576. 2010. 757605 https://doi.org/10.1117/12.842113
Cobos-Correa, Amanda ; Mall, Marcus A. ; Schultz, Carsten. / Reporters to monitor cellular MMP12 activity. Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II. Vol. 7576 2010.
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