Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-7-27
pubmed:abstractText
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.
pubmed:grant
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1873-6815
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
503-10
pubmed:dateRevised
2011-2-8
pubmed:meshHeading
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