CHOLESTEROL INDUCED VARIATIONS OF MEMBRANE DYNAMICS RELATED TO THE INDUCTION OF APOPTOSIS IN MOUSE THYMOCYTES

Purpose: To evaluate the involvement of cholesterol induced variations of membrane dynamics in mouse thymocyte apoptosis. Materials and meth ods: Membranes of thymocytes of RK mice were enriched with cholesterol using methyl-beta-cyclodextrins as carriers. Spontaneous apoptosis wa s compared with apoptosis induced either by X-irradiation, by treatmen t with dexamethasone (DEX), and by phorbol-12-myristate-13-acetate (PM A). Apoptotic cells were quantified by means of flow cytofluorometry. Results: Small amounts of incorporated cholesterol enhance the cellula r sensitivity for spontaneous apoptosis whereas larger amounts of inco rporated cholesterol protect against spontaneous apoptosis and apoptos is induced by irradiation, DEX, or PMA. Conclusions: Cholesterol exert s specific rigidity effects on lipid membranes which have been shown t o be involved in thymocyte apoptosis. The general effect of higher con centrations of cholesterol protecting against apoptosis hints towards a central protective mechanism. This study believes that either choles terol paralyses great parts of the cell metabolism or that the apoptot ic chain reaction is interrupted at a central point due to protection of membrane lipid regions from oxidative stress.