Mechanism of hemolysis induced by ferriprotoporphyrin IX.

Abstract

A B S T R A C T Incubation of a 0.5% suspension of washed, normal mouse erythrocytes with ferriprotoporphyrin IX (FP) at 37°C and pH 7.4 caused potassium loss, swelling, increased susceptibility to hypotonic lysis, and finally hemolysis. Hemolysis was not inhibited by incubation in the dark, malonyldialdehyde was not produced, and various free radical scavengers had no effect on the hemolysis. Only the sulfhydryl compounds, cysteine, dithiothreitol, and mercaptoethanol protected erythrocytes from FP. Potassium loss reached 90% within 30 min of exposure to 5 uM FP. This amount of FP caused >50% hemolysis within 2.5 h. Sucrose (0.1 M) completely prevented hemolysis but had no effect on potassium loss. Likewise, reducing the temperature from 37 to 25°C greatly retarded hemolysis but had no effect on potassium loss. These observations indicate that FP impairs the erythrocyte's ability to maintain cation gradients and induces hemolysis by a colloid-osmotic mechanism.

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

“…Hemin, the oxidized form of heme, causes hemolysis by inducing potassium loss and swelling of red cell membranes, destroying the ability of erythrocytes to maintain cation gradients [15]. There are two phases of the heme-induced hemolytic process: massive K + loss followed by depletion of glutathione and ATP, and massive hemoglobin loss [121]. In addition, hemin changes the conformation of cytoskeletal proteins and causes altered membrane stability and red cell lesions [15,122].…”

Interactions of hemin, antimalarial drugs and hemin-antimalarial complexes with phospholipid monolayers

“…Hemin can cause lysis of mouse [1,2] and human erythrocytes [3] and of malaria parasites [4,5]. Other types of cells were demonstrably resistant to this lytic effect (see Ref.…”

Enhancement of Heme-Induced Membrane Damage by the Anti-malarial Clotrimazole: the Role of Colloid-Osmotic Forces

“…The concentration dependence of the erythrocyte susceptibility to osmotic fragility agrees with previous studies. 27) However, in that work, 27) as low as 0.5 mM heme could increase the osmotic fragility, suggesting that mice erythrocytes are more susceptible to osmotic fragility than human erythrocytes. This could be due to differences in membrane composition known to exist between various White ghost membranes loaded with 5 mM heme or heme-CLT complex (5 mM heme-10 mM CLT) were incubated for 2 h at 37°C with or without 10 mM GSH and/or 10 mM CLT.…”

“…27) We therefore assessed the effect of heme and heme-CLT complex on the osmotic fragility of erythrocytes. We were unable to detect an increased susceptibility to hypotonic lysis at a low concentration of heme (3 mM), but at higher concentrations (10, 30 mM), heme enhanced osmotic fragility (Fig.…”