PDF(Pubmed)
Abstract：
S100B, a homodimeric Ca2+-binding protein, is produced and secreted by astrocytes, and its extracellular levels have been used as a glial marker in brain damage and neurodegenerative and psychiatric diseases; however, its mechanism of secretion is elusive. We used primary astrocyte cultures and calcium measurements from real-time fluorescence microscopy to investigate the role of intracellular calcium in S100B secretion. In addition, the dimethyl sulfoxide (DMSO) effect on S100B was investigated in vitro and in vivo using Wistar rats. We found that DMSO, a widely used vehicle in biological assays, is a powerful S100B secretagogue, which caused a biphasic response of Ca2+ mobilization. Our data show that astroglial S100B secretion is triggered by the increase in intracellular Ca2+ and indicate that this increase is due to Ca2+ mobilization from the endoplasmic reticulum. Also, blocking plasma membrane Ca2+ channels involved in the Ca2+ replenishment of internal stores decreased S100B secretion. The DMSO-induced S100B secretion was confirmed in vivo and in ex vivo hippocampal slices. Our data support a nonclassic vesicular export of S100B modulated by Ca2+, and the results might contribute to understanding the mechanism underlying the astroglial release of S100B.
摘要：
S100B,同二聚体Ca2+结合蛋白，由星形胶质细胞产生和分泌，其细胞外水平已被用作脑损伤和神经退行性疾病和精神疾病的神经胶质标记物；然而，其分泌机制难以捉摸。我们使用原代星形胶质细胞培养物和来自实时荧光显微镜的钙测量来研究细胞内钙在S100B分泌中的作用。此外,使用Wistar大鼠在体外和体内研究了二甲基亚砜（DMSO）对S100B的作用。我们发现DMSO,在生物测定中广泛使用的载体，是一个强大的S100B秘书处,这引起了Ca2+动员的双相反应。我们的数据表明，星形胶质细胞S100B的分泌是由细胞内Ca2的增加触发的，并表明这种增加是由于内质网的Ca2动员所致。此外，阻断质膜Ca2+通道参与Ca2+补充内储减少S100B分泌。在体内和离体海马切片中证实了DMSO诱导的S100B分泌。我们的数据支持Ca2调制的S100B的非经典囊泡输出，结果可能有助于理解S100B星形胶质细胞释放的潜在机制。
