Hu J, Van Eldik L J
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611, USA.
Biochim Biophys Acta. 1996 Oct 11;1313(3):239-45. doi: 10.1016/0167-4889(96)00095-x.
S100 beta is a calcium binding protein expressed primarily by astrocytes in the brain. In initiating studies of the toxic signalling pathways activated by high concentrations of S100 beta, we previously demonstrated that treatment of astrocytes with microM S100 beta results in a potent stimulation of the mRNA level and enzyme activity of inducible nitric oxide (NO) synthase, an enzyme previously implicated in glial pathology. We provide evidence here that NO formation stimulated by S100 beta can lead to cell death in astrocytes, with characteristics defined for apoptosis. Incubation of astrocytes with S100 beta for 48 h results in an increased percentage of astrocytes undergoing apoptotic cell death, as determined with the TUNEL technique, assays of DNA fragmentation and lactate dehydrogenase release. The cell death induced in responses to S100 beta addition correlates with the levels of NO formation, and an inhibitor of nitric oxide synthase attenuates the NO formation elicited by S100 beta, as well as the cell death. Therefore, we propose that S100 beta has the potential to be trophic or toxic. Although S100 beta may be involved in development, homeostasis and repair, chronic overexpression of the protein may mediate toxic responses or even cell death.
S100β是一种主要由大脑中的星形胶质细胞表达的钙结合蛋白。在启动对高浓度S100β激活的毒性信号通路的研究时，我们之前证明，用微摩尔浓度的S100β处理星形胶质细胞会强烈刺激诱导型一氧化氮（NO）合酶的mRNA水平和酶活性，该酶之前被认为与神经胶质病理有关。我们在此提供证据表明，S100β刺激产生的NO可导致星形胶质细胞死亡，具有凋亡所定义的特征。用TUNEL技术、DNA片段化分析和乳酸脱氢酶释放检测法测定，将星形胶质细胞与S100β孵育48小时会导致经历凋亡性细胞死亡的星形胶质细胞百分比增加。对添加S100β作出反应而诱导的细胞死亡与NO生成水平相关，一氧化氮合酶抑制剂可减弱S100β引发的NO生成以及细胞死亡。因此，我们提出S100β有可能具有营养作用或毒性作用。尽管S100β可能参与发育、体内平衡和修复，但该蛋白的慢性过度表达可能介导毒性反应甚至细胞死亡。
