IS HEMIN RESPONSIBLE FOR THE SUSCEPTIBILITY OF PLASMODIA TO OXIDANT STRESS

Based on the unusually high and stage-dependant susceptibility of Plas modia to oxidant stress it has been proposed that during parasite deve lopment, increasing levels of redox-active forms of iron are gradually released. The purpose of this study was to examine this proposal by u sing an assay monitoring the levels of available forms of iron for red ox reactions. Ascorbate-driven and iron-mediated degradation of advent itious DNA served as the basis for this functional assay. Incubation o f DNA with lysate from infected RBC caused massive degradation, which was dose, time- and parasite-stage dependent. In contrast, lysate from non-infected RBC did not induce DNA degradation. Likewise, lysate onl y from infected RBC enhanced the aerobic oxidation of ascorbate. These effects on both reactions, DNA degradation and ascorbate oxidation, c ould be reconstructed with hemin, instead of lysate. Also, chelators e xerted similar effects on both reactions. The results suggest that inc reased levels of redox-active forms of iron are liberated during paras ite development. We propose that hemin or hemin-like structures are th e appropriate candidates which could catalyze oxidative stress and der egulate the delicate redox balance of the host-parasite system.