title: Protein Disulfide Isomerase in Thrombosis.
abstract: Protein disulfide isomerase (PDI) is a 57-kDa oxidoreductase that facilitates cysteine thiol reactions inside and outside the cell. It mediates reduction or oxidation of protein disulfide bonds, thiol/disulfide exchange reactions, and transfer of NO from one protein thiol to another. It also has chaperone properties. PDI is actively secreted by most, if not all, of the cell types involved in thrombosis, binds to integrins on the cell surface, and circulates as a soluble protein in blood. It plays a critical role in thrombosis in mice and presumably the same role in human thrombosis. Eight proteins involved in thrombosis have been identified as PDI substrates; however, the role of this oxidoreductase in this process is not fully understood. Novel small-molecule PDI inhibitors have been developed and are being evaluated as antithrombotics in clinical trials. This combination of ongoing laboratory and clinical studies will greatly accelerate the pace of discovery and targeting of PDI function in thrombosis.
authors.affiliation: ACRF-Centenary Cancer Research Centre & NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: Joyce
authors.initials: J
authors.lastname: Chiu
authors.affiliation: St George Clinical School, St George Hospital, Kogarah, New South Wales, Australia.
authors.forename: Freda
authors.initials: F
authors.lastname: Passam
authors.affiliation: ACRF-Centenary Cancer Research Centre & NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: Diego
authors.initials: D
authors.lastname: Butera
authors.affiliation: ACRF-Centenary Cancer Research Centre & NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Hogg
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000097:blood*; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors / Q000097:blood*; D013927:Thrombosis / Q000097:blood* / Q000188:drug therapy
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019704:Protein Disulfide-Isomerases