Hypochlorous acid-induced membrane pore formation in red blood cells.
The hyperproduction of hypochlorous acid (HOCl), an extremely toxic biological oxidant generated by neutrophils and monocytes, is involved in the pathogenesis of many diseases. In these studies, we attempted to determine the membrane and cellular events associated with HOCl-induced erythrocyte impairment and haemolysis. In vitro human erythrocyte exposure to HOCl (0.1-1.0 mM) resulted in rapid oxidation of reduced glutathione, an increase in cell osmotic fragility and the formation of transient membrane pores. The process of glutathione oxidation depended on the [oxidant]/[cell number] ratio. The HOCl-induced haemolysis observed was apparently mediated by pore formation and altered membrane electrolyte permeability. The estimated pore radius was approximately 0.7 nm and the average number per cell was 0.01. The rate constant of HOCl-produced haemolysis depended on pH. There were significant differences in haemolysis of HOCl-treated erythrocytes which had maximal stability at pH 7.2-7.3.
Zavodnik
Leu B
LB
Institute of Biochemistry, National Academy of Sciences of Belarus, BLK-50, 230017 Grodno, Belarus. val@biochem.unibel.by
Zavodnik
Ilya B
IB
Lapshyna
Elena A
EA
Buko
Vjacheslav U
VU
Bryszewska
Maria J
MJ
D002463:Cell Membrane Permeability / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006997:Hypochlorous Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction
D016877:Oxidants; D006997:Hypochlorous Acid