Lipid peroxidation and myocardial ischaemic damage: cause or consequence?
Compelling evidence has been accumulated which indicates that myocardial tissue damage occurring during reperfusion after an ischaemic period may partly be due to the formation of oxygen free radicals and subsequent peroxidative processes. It has been well established that the actual toxicity of free radicals is dependent on the presence of free iron in the heart tissue. Based upon the hypothesis of McCord et al., proposing xanthine oxidase mediated formation of superoxide (O2-.) during the conversion of ATP-breakdown product(s) (hypo)xanthine to urate, we studied whether xanthine oxidase was able to mobilize free iron from the intra- and extracellular iron-binding proteins, ferritin and transferrin. It appeared that there was an O2-.-dependent and O2-.-independent mechanism by which xanthine oxidase could mobilize iron from ferritin while no iron mobilization from transferrin was detectable. The capacity of xanthine oxidase to mobilize iron from ferritin by an O2-.-independent mechanism implies that already during the anoxic/ischaemic period, iron may become available in the tissue which, upon the re-entrance of O2, catalyzes the formation of the very reactive OH radicals. The interaction between endothelial cells and cardiocytes in free radical homeostasis is discussed with the emphasis on the tissue localization of xanthine oxidase. The latter is located in endothelial cells implying an interaction between xanthine oxidase-induced endothelial cells initiated lipid peroxidation and the actual overall myocardial tissue damage.
Koster
J F
JF
Department of Biochemistry I, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
Biemond
P
P
Stam
H
H
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D003327:Coronary Disease / Q000209:etiology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005609:Free Radicals; D008054:Lipid Peroxides / Q000378:metabolism*; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism
D005609:Free Radicals; D008054:Lipid Peroxides; D010100:Oxygen