Oxidized molecules regulate pericellular proteolysis: Why antioxidants don't cut it....

[Guest guest]

I thought it was interesting that these biochemists are proposing that the regulation of a proteolytic enzyme in vivo is governed by oxidized products of myeloperoxidase.

They specifically state the following:

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"Many lines of evidence indicate that activated phagocytic cells inflict oxidative tissue injury in humans (1, 5, 20, 23). However, the results of clinical trials of antioxidants in the prevention of human disease have generally been disappointing (52). This observation raises the possibility that oxidants such as HOCl are also involved in suppressing inflammation. Our demonstration that HOCl restrains the proteolytic activity of cathepsin G may have important implications for understanding the role of

reactive intermediates in limiting tissue damage. Indeed, we have recently shown that HOCl inactivates matrilysin (MMP-7) by oxidatively cross-linking adjacent tryptophan and glycine residues in the catalytic domain of the enzyme (39, 40). This inactivation mechanism is distinct from the well studied mechanisms involving tissue inhibitors of metalloproteinases. Our findings suggest that local, pericellular production of HOCl by phagocytes is a physiological mechanism for governing proteinase activity during inflammation. The failure of antioxidants to prevent human inflammatory diseases in clinical trials may in part reflect a beneficial regulatory effect of oxidants in inflamed tissue. "

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J Biol Chem. 2005 Jun 20; [Epub ahead of print]

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=15967795

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T. pct35768@...

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