title: Serum iron increases with acute induction of hepatic heme oxygenase-1 in mice.
abstract: Heme oxygenase (HO)-1 is induced by oxidative stress and protects against oxidant injury. We examined the effect of rapid induction of hepatic HO-1 on serum iron level. Serum iron was approximately doubled within 6 h when HO-1 was induced by phenobarbital treatment of selenium-deficient mice. Blocking heme synthesis with diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) prevented the induction of HO-1 and the rise in serum iron. DDC did not block HO-1 induction by hemin. Inhibition of HO activity by tin protoporphyrin prevented a rise in serum iron that occurred following phorone treatment. These results indicate that heme synthesis or an exogenous source of heme is needed to allow induction of HO-1. Further, they link HO-1 induction with a rise in serum iron, suggesting that the iron resulting from catabolism of heme by HO-1 is released by the liver.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Volker
authors.initials: V
authors.lastname: Mostert
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakayama
authors.forename: Lori M
authors.initials: LM
authors.lastname: Austin
authors.forename: Ximena A
authors.initials: XA
authors.lastname: Levander
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Ferris
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Hill
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Burk
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004095:Dihydropyridines / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D006418:Heme / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D007501:Iron / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012643:Selenium / Q000172:deficiency