Iron homeostasis is maintained in the brain, but not the liver, following mild hypoxia.
Alterations in iron metabolism or oxidative damage in response to hypoxic incidents have been examined following re-oxygenation of the hypoxic tissue. To understand the consequences of decreased tissue oxygen on iron load, metal-catalyzed redox activity and oxidative modifications in isolation from re-oxygenation, the present study exposed mice to either normoxia, or mild hypoxia (380 Torr; approximately 10% normobaric oxygen) where the tissue was not allowed to re-oxygenate prior to examination. Brain, liver and skeletal muscle were examined for Fe3+ load, metal-catalyzed redox activity and oxidative modifications to proteins (N(epsilon)-(carboxymethyl)lysine), lipids (4-hydroxynonenal pyrrole) and nucleic acids (8-hydroxyguanosine). Hypoxia induced a 43% increase in the iron content of the liver (P < 0.001) as determined by ICP-MS and a 3.8-fold increase in Fe3+ load (P < 0.001) as determined by Perl's stain. There was a corresponding 2-fold increase in metal-catalyzed redox activity (P < 0.01) in the liver, but no change in the expression of oxidative markers. In contrast, non-significant increases in Fe3+ and metal-catalyzed redox activity were observed in the cerebral cortex, and molecular and granular layers of the hippocampus and cerebellum. Interestingly, hypoxia significantly decreased oxidative modifications to proteins and lipids, but not nucleic acids in most brain regions examined. In addition, hypoxia did not alter the Fe content of skeletal muscle, or the contents of Zn, Cu, Ni or Mn in liver, skeletal muscle, cerebral cortex or hippocampus. Together, these results indicate that there is a tighter regulation of iron metabolism in the brain than the liver, which limits the redistribution of Fe3+ following hypoxia.
Bishop
Glenda M
GM
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Smith
Mark A
MA
LaManna
Joseph C
JC
Wilson
Andrea C
AC
Perry
George
G
Atwood
Craig S
CS
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006706:Homeostasis; D000860:Hypoxia / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008670:Metals / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism
D008055:Lipids; D008670:Metals; D007501:Iron; D010100:Oxygen