Enhanced lipid oxidation by oxidatively modified myoglobin: role of protein-bound heme.
The formation of oxidized low density lipoprotein (LDL) is believed to play a significant role in the pathogenesis of atherosclerosis. Myoglobin in the presence of H(2)O(2) has been shown to catalyze LDL oxidation in vitro. It is established that an oxidatively altered form of myoglobin (Mb-H), which contains a prosthetic heme covalently crosslinked to the apoprotein, is a major product in the reaction of native myoglobin with peroxides. In the current study, we have shown for the first time that Mb-H, in the absence of exogenously added peroxides, oxidizes LDL and purified lipids, as determined by the formation of conjugated dienes, lipid peroxides, and thiobarbituric acid reactive substances. Moreover, the rate of oxidation of pure phosphatidylcholine by Mb-H was found to be at least sevenfold greater than that observed for native myoglobin. The current study strongly suggests a role for Mb-H in the lipid peroxidation observed with myoglobin.
Vuletich
J L
JL
Lipid Research Laboratory, Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel.
Osawa
Y
Y
Aviram
M
M
D000818:Animals; D002788:Cholesterol Esters / Q000737:chemistry; D006418:Heme / Q000378:metabolism; D006736:Horses; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009211:Myoglobin / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D009211:Myoglobin; D010743:Phospholipids; C099252:oxidized low density lipoprotein; D006418:Heme; D006861:Hydrogen Peroxide