title: Age-dependent increases in interstitial collagenase and MAP Kinase levels are exacerbated by superoxide dismutase deficiencies.
abstract: Many age-associated degenerative diseases commonly involve degradation of the extracellular matrix and aberrant matrix metalloproteinase-1 (MMP-1) expression. In diverse cell lines MMP-1 or interstitial collagenase (CL) expression is tightly regulated through a network of signals involving reactive oxygen species (ROS). However, whether the in vivo age-associated increase in CL expression is also sensitive to ROS-mediated signaling has not been established. To evaluate the contribution of ROS to the age-dependent increase in CL we monitored the levels of murine CL in two well-established models of oxidant stress. Analysis of murine CL levels in mice deficient in either of the intracellular superoxide dismutases (Sod2(+/-) or Sod1(-/-)) revealed its age- and redox-dependent expression relative to WT controls. Both age- and redox-dependent increases in murine CL expression were associated with elevations in phosphorylation of the MAP Kinases, Erk, JNK and p38. CL expression was highest in renal and skeletal muscle tissue from the aged Sod1(-/-) mice and was associated with a decrease in collagen staining. These findings suggest that MAPK signaling and CL production are both age- and redox-responsive. The redox sensitivity of age-associated CL expression suggests that degenerative disease associated with aberrant matrix remodeling and oxidant stress may be amenable to antioxidant-based therapies.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Dasgupta
authors.forename: Supriya
authors.initials: S
authors.lastname: Kar
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.forename: J Andres
authors.initials: JA
authors.lastname: Melendez
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1