title: The effect of N,N'-p-phenylenedimaleimide (PMD) on deoxygenation-induced K loss in sickle erythrocytes.
abstract: A variety of thiol reactive agents have been found to have antisickling properties thought to be due to the ability of these drugs to bind to hemoglobin, resulting in increased hemoglobin-oxygen affinity. Because thiol reactive agents also influence K movements in red cells and deoxygenation leads to K loss and Na gain in sickle erythrocytes, the authors investigated the possibility that deoxygenation-induced K loss could be influenced by thiol agents, independent of an effect on hemoglobin-oxygen affinity. Experiments were performed with the thiol crosslinking agent N,N'-p-phenylenedimaleimide (PMD). The authors found that PMD inhibited deoxygenation-induced K loss in sickle erythrocytes. This effect was not due to sickling inhibition as PMD-treated cells gained Na with deoxygenation, nor could the effect be explained by monofunctional PMD binding to membrane sulfhydryl groups, as a monofunctional analogue of PMD was not able to retard deoxygenation-induced K loss. These findings support a role for membrane sulfhydryl groups in deoxygenation-induced K movements in sickle red cells and suggest that this K loss may be prevented by crosslinking of certain membrane sulfhydryl groups.
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008301:Maleimides / Q000494:pharmacology*; D010100:Oxygen / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D008301:Maleimides; C011328:N,N'-4-phenylenedimaleimide; D011188:Potassium; D010100:Oxygen