Lysis of platelets and erythrocytes by the incorporation of a unique oxygenated sterol: 22R-hydroxycholesterol.
We have found that an oxygenated sterol, 22R-hydroxycholesterol [(22R)-5-cholestene-3 beta, 22-diol], lyses not only platelets but also erythrocytes in a dose-dependent manner. The lysis of platelets and erythrocytes were evidenced by the release of intracellular proteins, lactate dehydrogenase and hemoglobin, respectively. Their morphological change was shown by scanning electron microscopy. Elevated temperature was required for the lysis, probably to redistribute the sterol in the lipid bilayers in the plasma membranes. When the sterol was incorporated at low temperature, the temperature had to be raised to readily lyse cells. This lytic effect was, surprisingly enough, restricted to the R-isomer; the S-isomer was only marginally effective. Furthermore, sitosterol and other oxygenated sterols, with a hydroxyl group at different positions in the side chain of cholesterol, were much less lytic, regardless of the configuration of the hydroxyl group introduced. A possible mechanism for this interesting phenomenon will be discussed in relation with a structural alteration in lipid bilayers in plasma membranes brought about by the incorporation of this unique oxygenated sterol.
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000648:ultrastructure; D002417:Cattle; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects*; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D013261:Sterols / Q000494:pharmacology; D013329:Structure-Activity Relationship
D006888:Hydroxycholesterols; D013261:Sterols; C003585:22-hydroxycholesterol