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NF‐kB and caspases are involved in the hyaluronan and chondroitin‐4‐sulphate‐exerted antioxidant effect in fibroblast cultures exposed to oxidative stress
Author(s) -
Campo Giuseppe M.,
Avenoso Angela,
Campo Salvatore,
D'Ascola Angela,
Traina Paola,
Samà Dario,
Calatroni Alberto
Publication year - 2008
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1302
Subject(s) - oxidative stress , apoptosis , reactive oxygen species , microbiology and biotechnology , chemistry , fibroblast , caspase , dna damage , programmed cell death , proinflammatory cytokine , inflammation , biochemistry , biology , immunology , in vitro , dna
Oxidative stress, inflammation and apoptosis play a critical role in the onset and progression of cellular damage. It was previously reported that hyaluronan (HA) and chondroitin‐4‐sulphate (C4S) were able to protect human skin fibroblasts from oxidative stress. This antioxidant activity is due to the chelation of transition metal ions. Nuclear factor kB (NF‐kB), complexed with the inhibitory protein IkB α , is an ubiquitous response transcription factor involved in inflammatory reactions and acts by inducing cytokine expression, chemokines and cell adhesion molecules. Caspases are specific proteases responsible for the regulation and the execution of apoptotic cell death. The damage caused by free radicals may be amplified greatly by the activation of these factors. The study investigated whether the ability of these glycosaminoglycans (GAGs) to reduce oxidative damage in fibroblast cultures involves NF‐kB and caspases modulation. The treatment of fibroblasts with both HA and C4S limited the cell damage induced by FeSO 4 plus ascorbate. An interesting aspect of this treatment was that these GAGs significantly inhibited NF‐kB DNA binding, as confirmed by the normalization of IkB α protein, and reduced caspase activation at both mRNA and protein level. A possible explanation for these results, since lipid peroxidation intermediates may induce NF‐kB and caspase activation, is that HA and C4S indirectly blocked NF‐kB DNA binding and apoptosis by inhibiting reactive oxygen species (ROS) production. These data suggest that, during oxidative stress, HA and C4S may reduce cell damage by inhibiting NF‐kB and apoptosis activation as well as protecting cells from free radical attack. According to these finding the use of HA and C4S could be positive both as tool to clarify the exact mechanism of GAGs/ROS interaction, and also as drug therapy to reduce oxidative stress during inflammation. Copyright © 2007 John Wiley & Sons, Ltd.