Leak formation in human erythrocytes by the radical-forming oxidant t-butylhydroperoxide.
Oxidative damage of human erythrocytes by the lipoperoxide analogue, t-butylhydroperoxide, has been characterized with regard to ion-permeable leaks formed in the membrane. The formation of these leaks is not correlated with oxidative denaturation of hemoglobin and its precipitation at the membrane. It is also not related to the oxidation of membrane protein SH-groups. A close, although not simply proportional correlation could be demonstrated between leak formation and phospholipid peroxidation as monitored by occurrence of malondialdehyde. The two processes showed similar dependences on exposure time, concentration and temperature. Both were stimulated by the addition of azide as a ligand of ferric heme iron, and suppressed by the anti-oxidant, butylated hydroxytoluene. The leak pathway permits solute permeation with a temperature dependency of bulk diffusion in water and discriminates nonelectrolytes according to size. Discrimination among alkali chlorides corresponds to their free solution mobility; sodium halides are discriminated more effectively. Apparent radii of about 0.5-0.7 nm can be assigned to the defects, while apparent numbers of defects per cell as low as 0.1-0.2 suggest that the defects are dynamic in nature.
D001386:Azides / Q000494:pharmacology; D002463:Cell Membrane Permeability; D004910:Erythrocyte Membrane / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D010545:Peroxides / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013696:Temperature; D020122:tert-Butylhydroperoxide
D001386:Azides; D006454:Hemoglobins; D008054:Lipid Peroxides; D008563:Membrane Lipids; D010545:Peroxides; D010743:Phospholipids; D013438:Sulfhydryl Compounds; D008315:Malondialdehyde; D020122:tert-Butylhydroperoxide; D005947:Glucose