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Purified human chondroitin‐4‐sulfate reduced MMP/TIMP imbalance induced by iron plus ascorbate in human fibroblast cultures
Author(s) -
Campo Giuseppe M.,
Avenoso Angela,
Campo Salvatore,
D'Ascola Angela,
Ferlazzo Alida M.,
Samà Dario,
Calatroni Alberto
Publication year - 2006
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2005.08.009
Subject(s) - lipid peroxidation , oxidative stress , chemistry , fibroblast , biochemistry , matrix metalloproteinase , chondroitin sulfate , dna damage , in vitro , dna , glycosaminoglycan
Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs) is an important control point in tissue remodelling. Several findings have reported a marked MMP/TIMP imbalance in a variety of in vitro models in which oxidative stress was induced. Since previous studies showed that commercial hyaluronan and chondroitin‐4‐sulphate are able to limit lipid peroxidation during oxidative stress, we investigated the antioxidant capacity of purified human plasma chondroitin‐4‐sulfate in reducing MMP and TIMP imbalance in a model of ROS‐induced oxidative injury in fibroblast cultures. Purified human plasma chondroitin‐4‐sulfate was added to the fibroblast cultures exposed to FeSO 4 plus ascorbate. We assayed cell death, MMP and TIMP mRNA expression and protein activities, DNA damage, membrane lipid peroxidation, and aconitase depletion. FeSO 4 plus ascorbate produced severe death of cells and increased MMP‐1, MMP‐2 and MMP‐9 expression and protein activities. It also caused DNA strand breaks, enhanced lipid peroxidation and decreased aconitase. TIMP‐1 and TIMP‐2 protein levels and mRNA expression remain unaltered. Purified human plasma C4S, at three different doses, restored the MMP/TIMP homeostasis, increased cell survival, reduced DNA damage, inhibited lipid peroxidation and limited impairment of aconitase. These results further support the hypothesis that these biomolecules possess antioxidant activity and by reducing ROS production C4S may limit cell injury produced by MMP/TIMP imbalance.