Christ M, Luu B, Mejia J E, Moosbrugger I, Bischoff P
Laboratoire de Chimie Organique des Substances Naturelles, URA CNRS no. 31, Strasbourg, France.
Immunology. 1993 Mar;78(3):455-60.
Oxygenated derivatives of cholesterol (oxysterols), a family of naturally occurring compounds, possess marked anti-proliferative and immunosuppressive activities, in particular they have been shown to inhibit T-cell responses to different stimuli. 25-Hydroxycholesterol (25-OHC) and 7 beta,25-dihydroxycholesterol (7.25-OHC) are able to kill not only RDM4 murine lymphoma in vitro, but also, surprisingly, mouse thymocytes after several hours of incubation. In this study, we report that the death of RDM4 and thymocytes induced by oxysterols exhibits the features of apoptosis. This phenomenon was identified by agarose gel electrophoresis of DNA fragments extracted from the cells and quantified by flow cytometric analysis of the DNA fluorescence of propidium iodide-stained cells. Cycloheximide and actinomycin D were found to decrease the number of apoptotic cells and to increase cell viability, indicating a requirement for the synthesis of macromolecules in oxysterol-induced programmed cell death. The pathway by which 25-OHC and 7.25-OHC are able to induce apoptosis in this type of cell and the possible contribution of these compounds to thymus involution during development are discussed.
胆固醇的氧化衍生物（氧化甾醇）是一类天然存在的化合物，具有显著的抗增殖和免疫抑制活性，特别是已显示它们能抑制T细胞对不同刺激的反应。25-羟基胆固醇（25-OHC）和7β,25-二羟基胆固醇（7,25-OHC）不仅能够在体外杀死RDM4鼠淋巴瘤细胞，而且令人惊讶的是，在孵育数小时后还能杀死小鼠胸腺细胞。在本研究中，我们报告氧化甾醇诱导的RDM4细胞和胸腺细胞死亡表现出凋亡特征。这种现象通过对从细胞中提取的DNA片段进行琼脂糖凝胶电泳来鉴定，并通过对碘化丙啶染色细胞的DNA荧光进行流式细胞术分析来定量。发现放线菌酮和放线菌素D可减少凋亡细胞数量并提高细胞活力，表明在氧化甾醇诱导的程序性细胞死亡中需要合成大分子。讨论了25-OHC和7,25-OHC能够在这类细胞中诱导凋亡的途径以及这些化合物在发育过程中对胸腺退化可能的作用。
