Hemoglobin (Hb), naturally guarded in red blood cells, leaks to plasma under many circumstances. Hb has been found to exhibit profound peroxidative reactivity towards low-density lipoprotein (LDL). much higher than the enzyme horseradish peroxidase (HRP). Besides oxidation of LDL lipids, crosslinking of apoprotein B is characteristic for Hb-derived LI)L oxidation. These results suggest that plasma Hb should be considered as an atherogenic factor. The present study evaluated three potential mechanisms by which Hb exerts its peroxidative potential towards LDL: (1) LDL-bound heroin, which transfers from per0xidated Hb, is the oxidizer; (2) H202-activated Hb operates as a peroxidase enzyme via its heme active site; (3) a heine-initiated globin radical of tlb launches a cascade of radicals on LDL protein or/and lipids. Only insignificant heme transfer from Hb to LI)L was found to occur concomitantly with LDL oxidation. In addition, LDL was oxidized faster by hemoglobin than by free heroin. These data ruled out mechanism (1). While tile level of tI202activated ferryl state of HRP was consumed in the process of LDL peroxidation, that of Hb was not. In addition, inhibition of Hb-derived LDL oxidation was not followed by reduction of Hb ferryl level. Under the conditions of inhibited LDI, oxidation, Hb-medlated peroxidation of guaiacol remained unchanged. These data excluded mechanism (2). We conclude that mechanism (3) might operate. It is suggested that the globin radical initiates a cascade of ape B radicals which are terminated by protein crosslinking. These findings are important for understanding the mechanism of lib-derived damage of vascular components.
|Published - 1997