Intracellular ferriprotoporphyrin IX is a lytic agent

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Abstract

Human erythrocytes were treated with menadione to oxidatively denature hemoglobin and release ferriprotoporphyrin IX (ferriheme, FP) intracellularly. The high affinity of FP for chloroquine was used to detect its release. After incubation for 1 hr at 37°C and pH 7.4 with 0.5 mM menadione, erythrocytes bound 14C-chloroquine with an apparent dissociation constant of 10-6 M. Untreated erythrocytes did not bind chloroquine with high affinity. At a chloroquine concentration in the medium of 2 μM, for example, menadione-treated erythrocytes bound 70 μmole chloroquine/kg and untreated erythrocytes bound 13.4 μmole/kg. The intracellular location of FP released by menadione was verified by finding that Tween 80 did not prevent chloroquine binding. By contrast, Tween 80 inhibited the binding of chloroquine to erythrocytes treated with extracellular FP. The hemolytic response to menadione was characteristic of the hemolytic response to FP. Thus, 5 μM chloroquine caused hemolysis to increase to 60% from baseline values of 5% in experiments using erythrocytes treated either with 0.5 mM menadione or with 5 μM FP; and, in both cases, the potentiating effect of chloroquine was inhibited by 1 μM mefloquine or 10 μM quinine. Higher concentrations of menadione caused hemolysis in the absence of chloroquine. We conclude that FP released by menadione exists intracellularly in a form that is accessible to bind chloroquine and to express its lytic activity.

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APA

Fitch, C. D., Chevli, R., Kanjananggulpan, P., Dutta, P., Chevli, K., & Chou, A. C. (1983). Intracellular ferriprotoporphyrin IX is a lytic agent. Blood, 62(6), 1165–1168. https://doi.org/10.1182/blood.v62.6.1165.bloodjournal6261165

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