Plasminogen activator inhibitor 2 (PAI-2) is not inactivated by exposure to oxidants which can be released from activated neutrophils.
Purified recombinant human monocyte plasminogen activator inhibitor 2 (PAI-2) retained inhibitory activity after exposure to a number of oxidants, including hypochlorite anion (OCl-), chloramine-T (CT) and hydrogen peroxide (H2O2). Analysis of PAI-2 exposed to oxidants by gel filtration chromatography and SDS-PAGE indicated that although the protein could no longer be detected by silver staining, this was not due to fragmentation of the PAI-2 molecule. The sensitivity of a number of serine protease inhibitors (serpins), (eg. alpha 1 proteinase inhibitor (alpha 1PI) and plasminogen activator inhibitor 1 (PAI-1] to oxidative inactivation has been attributed to oxidation of reactive site methionine residues and/or tertiary structural modifications. The relevance of these phenomena and the potential for PAI-2 to be used as a therapeutic inhibitor of urokinase (uPA)-dependent proteolysis during inflammation and tumour metastasis is discussed.
Baker
M S
MS
Division of Clinical Sciences, JCSMR, Australian National University, Canberra.
Green
S P
SP
Goss
N
N
Katrantzis
M
M
Doe
W F
WF
D000595:Amino Acid Sequence; D002700:Chloramines / Q000494:pharmacology; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology*; D010084:Oxidation-Reduction; D015849:Plasminogen Inactivators / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014105:Tosyl Compounds
D002700:Chloramines; D015849:Plasminogen Inactivators; D015843:Serpins; D014105:Tosyl Compounds; C016300:chloramine-T; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide