The superoxide dismutase-mimic copper-putrescine-pyridine suppresses lipid peroxidation in CHO cells. Implications for its prooxidative and antioxidative mechanisms of action.
Copper-Putrescine-Pyridine (Cu-PuPy) is a membrane-permeable complex which efficiently dismutates superoxide. In excess of 0.1 mM it is highly cytotoxic and oxidizes cellular GSH with concomitant production of H2O2. Here we show that treatment of CHO cells with 0.2 mM Cu-PuPy (0-200 min) leads to an accumulation of H2O2. Organic hydroperoxides which are also formed at low levels in the present of Cu-PuPy, increase significantly after removal of the copper complex. We conclude that Cu-PuPy acts as an oxidant until cellular GSH is depleted. However, by interfering with radical chain propagation reactions, it suppresses lipid peroxidation and thus substitutes for consumed physiological antioxidants in a later stage of treatment. This consistently explains our previous, seemingly paradox, finding that longer Cu-PuPy treatments may be significantly les toxic than shorter ones.
Nagele
A
A
Strahlenbiologisches Institut, Ludwig-Maximilians-Universität, München, Germany.
Lengfelder
E
E
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016466:CHO Cells / Q000378:metabolism*; D006224:Cricetinae; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D009942:Organometallic Compounds / Q000494:pharmacology*; D012545:Schiff Bases / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*
D000975:Antioxidants; D009942:Organometallic Compounds; D012545:Schiff Bases; C064004:N,N'-bis(2-pyridylmethylene)-1,4-butanediamine (N,N',N'',N''')-Cu(II)diperchlorate; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase