Metal ion interactions in the control of haem oxygenase induction in liver and kidney.
Mn2+ and Zn2+ exhibit a striking ability to block the induction by Sn2+ and Ni2+ of haem oxygenase (EC 1.14.99.3) in kidney. The blocking effects of Mn2+ and Zn2+ were found to be greatest on simultaneous administration, time-dependent when administered up to 8 h before the inducing metal ions, and ineffective when administered as little as 10 min after the inducing metal ions. The decreases in cytochrome P-450 and haem contents and the sequential changes in delta-aminolaevulinate synthase (EC 2.3.1.37) activity that occur concomitant with haem oxygenase induction were largely eliminated with simultaneous or prior treatment with Mn2+ or Zn2+, but not when Mn2+ or Zn2+ was administered after Sn2+ or Ni2+. Mn2+ and Zn2+ did not increase the catabolism of the enzyme in vivo. Zn2+ on simultaneous administration was also able substantially to block the induction of haem oxygenase by Co2+, Cd2+ and Ni2+ in liver. The Zn2+ blockade of Cd2+ induction was examined in detail, and prior or simultaneous administration of Zn2+ was found to be effective in blocking the induction of haem oxygenase and the concomitant decreases in cytochrome P-450 and haem contents, ethylmorphine demethylase activity and the sequential changes in delta-aminolaevulinate synthase activity. Zn2+ administration 10 min or more after Cd2+ was ineffective in preventing the occurrence of these perturbations in haem metabolism. These findings describe a new and striking biological property of Mn2+ and Zn2+, and indicate the existence of significant metal ion interactions in the control of haem metabolism.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D051381:Rats; D015032:Zinc / Q000494:pharmacology*
D002413:Cations, Divalent; D006418:Heme; D008345:Manganese; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase; D015032:Zinc