Oxidative stress of human erythrocytes by iodate and periodate. Reversible formation of aqueous membrane pores due to SH-group oxidation.
Human erythrocytes were exposed to oxidative stress by iodate and periodate. Oxidation causes a time- and concentration-dependent increase in membrane permeability for hydrophilic molecules and ions. The induced leak discriminates nonelectrolytes on the basis of molecular size and exhibits a very low activation energy (Ea = 1-4 kcal.mol-1). These results are reconcilable with the formation of aqueous pores. The pore size was approximated to be between 0.45 and 0.6 nm. This increase in permeability is reversible upon treatment with dithioerythritol. Blocking of membrane thiol groups with N-ethylmaleimide protects the membranes against leak formation. The oxidation causes dithioerythritol-reversible modification of membrane proteins as indicated by the gel electrophoretic behavior. These modifications can also be suppressed by blocking the membrane thiol groups with N-ethylmaleimide. About half of the membrane methionine is oxidized to acid hydrolysis-stable derivatives. A fast saturating increase in diene conjugation was observed in whole cells but not in isolated membranes, with only minor degradation of fatty acid chains. The oxidation of cell membrane lipids as well as oxidation of cell surface carbohydrates are not involved in leak formation. Taken together with earlier data (Deuticke, B., Poser, B., Lütkemeier, P. and Haest, C.W.M. (1983) Biochim. Biophys. Acta 731, 196-210), these findings indicate that formation of disulfide bonds by different oxidative mechanisms results in leaks with similar properties.
D002241:Carbohydrates / Q000097:blood; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004220:Disulfides / Q000097:blood; D004226:Dithioerythritol / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D005033:Ethylmaleimide / Q000494:pharmacology; D006801:Humans; D007452:Iodates / Q000494:pharmacology*; D007455:Iodine / Q000494:pharmacology*; D008563:Membrane Lipids / Q000097:blood; D008565:Membrane Proteins / Q000097:blood; D010084:Oxidation-Reduction; D010504:Periodic Acid / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000097:blood*
D002241:Carbohydrates; D004220:Disulfides; D007452:Iodates; D008563:Membrane Lipids; D008565:Membrane Proteins; D013438:Sulfhydryl Compounds; D010504:Periodic Acid; D004226:Dithioerythritol; C034670:iodic acid; D007455:Iodine; C009288:metaperiodate; D005033:Ethylmaleimide