Intracellular redistribution of heme in rat liver under oxidative stress: the role of heme synthesis.
Heme distribution in subcellular fractions of rat liver was studied first hours under the action of several agents causing oxidative stress in vivo. Total and post-mitochondrial heme content in liver was found to depend on both the level of hemolysis products in blood and agent's capacity to modify heme and hemoproteins. The increase of activity of 5-aminolevulinate synthase (ALAS) and/or heme accumulation in mitochondria was accompanied by increase of tryptophan-2,3-dioxygenase (TDO) heme saturation. Membrane stabilisation by tocopherol or prevention of early ALAS induction by cycloheximide prevented both mitochondrial heme accumulation and increase of TDO heme saturation. Modification of heme fully prevented the alterations of total heme content even under severe hemolysis as well as the increase of TDO heme saturation if no increase of heme synthesis occurred. Thus heme synthesis can greatly contribute to heme intracellular redistribution under oxidative stress.
Kaliman
Pavel A
PA
Biochemistry Department, Kharkiv National University, 61077 Kharkiv, Ukraine. pavel.a.kaliman@univer.kharkov.ua
Barannik
Tatyana
T
Strel'chenko
Ekaterina
E
Inshina
Natalya
N
Sokol
Oxana
O
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005990:Glycerol; D006418:Heme / Q000096:biosynthesis / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010659:Phenylhydrazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014494:Unithiol / Q000494:pharmacology
D010659:Phenylhydrazines; C030299:phenylhydrazine; D014494:Unithiol; D006418:Heme; D003513:Cycloheximide; D006861:Hydrogen Peroxide; D014366:Tryptophan Oxygenase; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase; D005978:Glutathione; D005990:Glycerol