title: Reactivity of active center analogs of Cu2Zn2 superoxide dismutase on activated polymorphonuclear leukocytes.
abstract: In unseparated human blood the Cu2Zn2 superoxide dismutase mimetic reactivity of several differently coordinated low Mr copper chelates on TPA-activated polymorphonuclear leukocytes was evaluated and compared to their apo-chelates, CuSO4, and the native enzyme. Similar to intact superoxide dismutase, 350-400 nM Cu flexibly complexed in a di-Schiff base mode in CuPu(Py)2 and CuPu(Im)2, respectively, was sufficient to inhibit the oxidative burst-dependent superoxide production of human blood phagocytes by 50%. Acetate- or biuret-type copper chelates behaved like CuSO4. The catalytic superoxide dismuting reactivity of the di-Schiff base active center analogs of SOD was confirmed using isolated porcine PMNs. Even in the presence of 600 microM albumin as a model for competitive copper chelation in biological fluids CuPu(Py)2 and CuPu(Im)2 remained active. The stability during the Cu(I)/Cu(II) redox cycling was demonstrated in the presence of activated PMNs and albumin, taking advantage of the electron paramagnetic properties of CuPu(Py)2 and CuPu(Im)2.
authors.affiliation: Anorganische Biochemie Physiologisch-Chemisches Institut, Universität Tübingen, F.R.G.
authors.forename: R
authors.initials: R
authors.lastname: Miesel
authors.forename: H J
authors.initials: HJ
authors.lastname: Hartmann
authors.forename: Y J
authors.initials: YJ
authors.lastname: Li
authors.forename: U
authors.initials: U
authors.lastname: Weser
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001665:Binding Sites; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000097:blood; D004795:Enzyme Stability; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000201:enzymology* / Q000502:physiology; D012545:Schiff Bases; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000097:blood* / Q000494:pharmacology; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002614:Chelating Agents; D012545:Schiff Bases; D012710:Serum Albumin, Bovine; D003300:Copper; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate