Brawer J R, Small L, Wang X, Schipper H M
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Neurotoxicology. 1995 Summer;16(2):327-36.
An unusual population of astrocytes containing Gomori-positive inclusions occurs in periventricular regions of the brain in all mammalian species. The inclusions are autofluorescent and exhibit non-enzymatic peroxidase activity. Estradiol treatment in vivo and cysteamine treatment in vitro have been shown to increase the number and size of these inclusions. Recent studies indicate that the Gomori inclusions are accumulations of autophagocytized abnormal mitochondria. The mitochondrial changes initiating Gomori inclusion formation begin with a loss of cristae. Energy dispersive X-ray microanalysis also reveals small emission peaks indicative of chromium. The appearance of chromium peaks in the initial stages of mitochondrial transformation suggests that enhanced permeability to chromium could play a causal role in generating Gomori inclusions. In the present study, we have examined the uptake and intracellular distribution of chromium during Gomori inclusion formation in cysteamine-treated cultured astrocytes. 51Cr was added to the media of glial cultures 24 hours prior to the initiation of the formation of Gomori inclusions by the addition of cysteamine. Cultures were fixed and prepared for EM radioautography at 12, 24, and 72 hours following the addition of cysteamine. 51Cr was added to control cells but they were not treated with cysteamine, and, they did not, therefore, develop Gomori inclusions. Cysteamine exposure resulted in a rapid sustained increase in radiolabel over the astrocytes. Much of the label was concentrated over mitochondria. At the late time points, label concentrated progressively over developing Gomori inclusions. These results confirm that the onset of Gomori inclusion formation coincides with increase cellular permeability to chromium and they indicate that uptake of chromium by mitochondria may play an important role in initiating development of these structures.
在所有哺乳动物物种的脑室周围区域，存在着一群不同寻常的星形胶质细胞，其含有Gomori阳性包涵体。这些包涵体具有自发荧光，并表现出非酶促过氧化物酶活性。体内雌二醇处理和体外半胱胺处理已被证明可增加这些包涵体的数量和大小。最近的研究表明，Gomori包涵体是自噬异常线粒体的积累。引发Gomori包涵体形成的线粒体变化始于嵴的丧失。能量分散X射线微分析还揭示了指示铬的小发射峰。线粒体转变初始阶段铬峰的出现表明，对铬通透性的增强可能在产生Gomori包涵体中起因果作用。在本研究中，我们检测了在半胱胺处理的培养星形胶质细胞中Gomori包涵体形成过程中铬的摄取和细胞内分布。在通过添加半胱胺启动Gomori包涵体形成前24小时，将51Cr添加到神经胶质培养物的培养基中。在添加半胱胺后的12、24和72小时，将培养物固定并制备用于电子显微镜放射自显影。将51Cr添加到对照细胞中，但它们未用半胱胺处理，因此，它们未形成Gomori包涵体。半胱胺暴露导致星形胶质细胞上放射性标记迅速持续增加。大部分标记集中在线粒体上。在后期时间点，标记逐渐集中在正在形成的Gomori包涵体上。这些结果证实，Gomori包涵体形成的开始与细胞对铬通透性的增加同时发生，并且表明线粒体对铬的摄取可能在启动这些结构的发育中起重要作用。
