Reactivity of active center analogs of Cu2Zn2 superoxide dismutase on activated polymorphonuclear leukocytes.
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.
Miesel
R
R
Anorganische Biochemie Physiologisch-Chemisches Institut, Universität Tübingen, F.R.G.
Hartmann
H J
HJ
Li
Y J
YJ
Weser
U
U
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002614:Chelating Agents; D012545:Schiff Bases; D012710:Serum Albumin, Bovine; D003300:Copper; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate