title: Tissue- and cell-specific co-localization of intracellular gelatinolytic activity and matrix metalloproteinase 2.
abstract: Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme that degrades extracellular matrix proteins. Recent studies indicate that MMP-2 also has a role in intracellular proteolysis during various pathological conditions, such as ischemic injuries in heart and brain and in tumor growth. The present study was performed to map the distribution of intracellular MMP-2 activity in various mouse tissues and cells under physiological conditions. Samples from normal brain, heart, lung, liver, spleen, pancreas, kidney, adrenal gland, thyroid gland, gonads, oral mucosa, salivary glands, esophagus, intestines, and skin were subjected to high-resolution in situ gelatin zymography and immunohistochemical staining. In hepatocytes, cardiac myocytes, kidney tubuli cells, epithelial cells in the oral mucosa as well as in excretory ducts of salivary glands, and adrenal cortical cells, we found strong intracellular gelatinolytic activity that was significantly reduced by the metalloprotease inhibitor EDTA but not by the cysteine protease inhibitor E-64. Furthermore, the gelatinolytic activity was co-localized with MMP-2. Western blotting and electron microscopy combined with immunogold labeling revealed the presence of MMP-2 in different intracellular compartments of isolated hepatocytes. Our results indicate that MMP-2 takes part in intracellular proteolysis in specific tissues and cells during physiological conditions.
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors.forename: Ann Iren
authors.initials: AI
authors.lastname: Solli
authors.forename: Bodil
authors.initials: B
authors.lastname: Fadnes
authors.forename: Jan-Olof
authors.initials: JO
authors.lastname: Winberg
authors.forename: Lars
authors.initials: L
authors.lastname: Uhlin-Hansen
authors.forename: Elin
authors.initials: E
authors.lastname: Hadler-Olsen
mesh_terms: D000818:Animals; D004492:Edetic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005780:Gelatin / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D059748:Proteolysis / Q000187:drug effects
chemical_list: D005780:Gelatin; D004492:Edetic Acid; D020778:Matrix Metalloproteinase 2
keywords: MMP-2; gelatinolytic activity; homeostasis; intracellular