Plasminogen activator-inhibitor , oxidative inactivation

The sensitivity of many serine-protease inhibitors (serpins) to ROIs has been determined in a number of groups and is summarized in Table 2. Of these serine-protease inhibitors, the most sensitive to inactivation by oxidants like OC1- or chloramines are those which contain methionine at or juxtaposed to the reactive centre [49] (e.g. plasminogen activator-inhibitor-1 (PAI-1), oq-proteinase inhibitor and 0(2-antiplasmin). Inactivation is thought to principally be due to the oxidation of these methionine residues to methionine sulfoxide [50-52]. PAI-1, which is rapidly inactivated in plasma, is also extremely sensitive to oxidants like iV-chlorosuccinimide, chloramine-T and H2O2, through a reaction involving oxidation of the reactive-site methionine. 

Since aiAT represents the archetype for the serpin (serine-proteinase inhibitor) superfamily of proteins, it is possible that similar oxidative or proteolytic mechanisms may function in the inactivation of other serpins that are important in controlling the inflammatory cascade. Some serpins contain a readily oxidised reactive-centre methionine residue (e.g. plasminogen activator-inhibitor [108] and a2-antiplasmin [109]), whilst all serpins (including antithrombin III [110] and protease nexin I [111]) contain an exposed loop which is susceptible to cleavage by proteinases. 

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