Enhanced lipid oxidation by oxidatively modified myoglobin: role of protein-bound heme

Biochem Biophys Res Commun. 2000 Mar 24;269(3):647-51. doi: 10.1006/bbrc.2000.2349.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cholesterol Esters / chemistry
  • Heme / metabolism
  • Horses
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • Kinetics
  • Lipoproteins, LDL / blood*
  • Lipoproteins, LDL / chemistry
  • Lipoproteins, LDL / drug effects
  • Lipoproteins, LDL / metabolism*
  • Myoglobin / drug effects
  • Myoglobin / metabolism
  • Myoglobin / pharmacology*
  • Oxidation-Reduction
  • Phospholipids / chemistry

Substances

  • Cholesterol Esters
  • Lipoproteins, LDL
  • Myoglobin
  • Phospholipids
  • oxidized low density lipoprotein
  • Heme
  • Hydrogen Peroxide