Role of hemopexin in protection of low-density lipoprotein against hemoglobin-induced oxidation.
Globin-free hemin and certain hemoproteins, predominantly hemoglobin, are active triggers of low-density lipoprotein (LDL) peroxidation, a contributing cause of atherosclerosis. The role of the plasma heme-binding protein, hemopexin, in protecting apolipoprotein B and LDL lipids from oxidation triggered by either hemin or hemoglobin in the presence of low amounts of H2O2, was investigated at physiological pH and temperature. Significantly, hemopexin prevented not only hemin-mediated modification of LDL but also LDL peroxidation induced by hemoglobin, both by met and oxy forms. Analysis of the data revealed that the rate of heme transfer from methemoglobin to hemopexin was highly dependent upon temperature: only minimal heme transfer occurred at 20 degrees C, whereas at the physiological temperature of 37 degrees C, heme transfer was rapid, within the lag phase of LDL oxidation, regardless of the presence or absence of H2O2. Heme did transfer to hemopexin from oxyhemoglobin as well, but only in the presence of H2O2. The proposed mechanism of the inhibition of oxyhemoglobin oxidative reactivity by hemopexin involves peroxidation of oxyhemoglobin (Fe(II)) to ferrylhemoglobin (FeIV), followed by a comproportionation reaction (FeIV+FeII-->2FeIII), yielding methemoglobin (FeIII) from which heme is readily transferred to hemopexin. Taken together, the data demonstrate that hemopexin can act as an extracellular antioxidant against hemoglobin-mediated damage in inflammatory states, which is especially important when haptoglobin is depleted or absent.
Miller
Y I
YI
Faculty of Medicine, Tel Aviv University, Israel.
Smith
A
A
Morgan
W T
WT
Shaklai
N
N
D000975:Antioxidants / Q000494:pharmacology; D001055:Apolipoproteins B / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006418:Heme / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006466:Hemopexin / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008706:Methemoglobin / Q000378:metabolism; D008956:Models, Chemical; D010084:Oxidation-Reduction; D013053:Spectrophotometry; D013696:Temperature; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D001055:Apolipoproteins B; D006454:Hemoglobins; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D006418:Heme; D008706:Methemoglobin; D006466:Hemopexin; D006861:Hydrogen Peroxide