REVIEW: Methionine Sulfoxide and the Oxidative Regulation of Plasma Proteinase Inhibitors

Abstract

The sensitivity of methionine residues to oxidation is a mechanism by which many proteins, including plasma proteinase inhibitors, may be oxidatively inactivated. Much evidence suggests that methionine oxidation and concurrent losses of protein activity not only occur widely in living systems but are physiologic, homeostatic processes. Neutrophils, macrophages and other leukocytes secrete large quantities of powerful oxidants at sites of inflammation and may readily bring about methionine oxidative inactivation of proteins. In particular, oxidation of proteinase inhibitors may favorably alter the proteinase-antiproteinase balance to facilitate tissue remodeling and protection from invading organisms. Leukocyte-mediated inhibitor oxidation also appears to regulate local immunosuppressive activity. Pathophysiologic processes such as emphysema and rheumatoidal disease involve derangements of these homeostatic mechanisms.

Silencing of the methionine sulfoxide reductase A gene results in loss of mitochondrial membrane potential and increased ROS production in human lens cells

“…In cataract, as much as 60% of membrane bound protein methionines are found as Met(O) (Truscott and Augusteyn, 1977;Garner and Spector, 1980) providing an association between methionine oxidation and cataract development. Met(O) formation is known to cause loss of protein and subsequent cellular function (Brot et al, 1981;Caldwell et al, 1978;Ciorba et al, 1997;Johnson and Travis, 1979;Vogt, 1995;Swaim and Pizzo, 1988) that could be detrimental to lens homeostasis and be a causative factor in cataract formation.…”

Up-regulation of defense enzymes is responsible for low reactive oxygen species in malignant prostate cancer cells

“…ROS can specifically damage certain protease inhibitors, including 1-proteinase inhibitor and 2-macroglobulin, plasminogen activator inhibitor and 2-plasmin inhibitor by oxidizing methionine residues in the active sites (Swaim and Pizzo, 1988). Resultant inactivation of these protein inhibitors could enhance actions of proteases, such as elastase, plasminogen activator and plasmin (Szatrowski and Nathan, 1991), which may facilitate tumor invasion and metastasis.…”

Oxidized mucus proteinase inhibitor: a fairly potent neutrophil elastase inhibitor

“…This chemical modification becomes biologically significant when it affects the activity of proteins. Thus, a number of hormones, chemotactic factors, proteinases and proteinase inhibitors undergo partial or total oxidative inactivation (for a review see Swaim and Pizzo, 1988).…”