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DEGRADATION OF CYSTATIN C BY MATRIX METALLOPROTEINASES‐2 AND ‐9 AND ITS INHIBITION BY DOXYCYCLINE OR SELENIUM
Author(s) -
KOKSOY ASLIHAN
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.617.10
Subject(s) - matrix metalloproteinase , cystatin c , chemistry , oxidative stress , reactive oxygen species , selenium , pharmacology , cysteine , biochemistry , enzyme , medicine , creatinine , organic chemistry
Matrix metalloproteinases (MMPs) are proteinases with a wide range of intra and extracellular targets. MMP‐2 and ‐9 are the major MMPs in the circulation which can get activated by oxidants. Cystatin C (CysC), is a very potent inhibitor cysteine proteinases. Decreased CysC levels and increased activity of MMPs are commonly observed in diseases involving chronic oxidative and inflammatory stress such as arteriosclerosis, abdominal aortic aneurisms and multiple sclerosis. In our study we hypothesized that CysC could be a substrate for these enzymes as an explanation for the observed reduction in CysC levels in these diseases. CysC has a common cleavage motif that can be recognized by both MMP‐2 and 9. Cleavage of CysC at this site have been shown to result in amyloid formation in neural tissue. We found that CysC is degraded by both MMPs ‐2 and ‐9, by 71±6% and 78±1% respectively, after 4 hours of incubation. Pre‐treatment of the cells with selenium (an essential biological trace element) or doxycyclin (an MMP inhibitor) prevented MMP‐induced degradations, significantly. Our preliminary data suggest interaction between CysC and MMPs can be modulated with reactive oxygen species and provide grounds for a new hypothesis for explaining amyloid formation associated with oxidant stress related pathologies.