Gartner W, Lang W, Leutmetzer F, Domanovits H, Waldhäusl W, Wagner L
Department of Medicine III, Division of Clinical Endocrinology and Metabolism, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Cereb Cortex. 2001 Dec;11(12):1161-9. doi: 10.1093/cercor/11.12.1161.
Recently we identified a novel EF-hand Ca-binding protein termed secretagogin, which is expressed in neuroendocrine cells. Immunohistochemical investigations, using a murine monoclonal and an affinity purified rabbit polyclonal anti-secretagogin antibody as well as Northern-blot and Western-blot analysis revealed a neuron-specific cerebral expression pattern. Secretagogin was detected in high quantity in basket and stellate cells of the cerebellar cortex, in secretory neurons of the anterior part of the pituitary gland and in singular neurons of the frontal and parietal neocortex. Remarkable staining intensity was observed in hypothalamic and in hippocampal neurons. Using a newly developed sandwich capture ELISA we show presence of secretagogin in serum of patients suffering from hypoxic neuronal damage. In sera obtained from 32 patients with different forms of neurological symptoms due to focal cerebral ischemia, secretagogin levels ranged from 3 to 236 pg/ml, with highest levels observed on days 2 and 3 after infarction. Three patients exhibiting minor, reversible neurological deficits had nondetectable serum secretagogin levels at time points of testing. In 50 control sera, secretagogin was below the detection limit of our ELISA. Parallel analysis of secretagogin and the established neurobiochemical marker S-100B in 14 representative patients revealed comparable results. However, S-100B levels were higher and exhibited different kinetics than secretagogin. Our data present the cerebral expression pattern of secretagogin and give evidence that this protein might represent a clinically relevant serum marker indicative for neuronal damage.
最近，我们鉴定出一种名为分泌粒蛋白的新型EF手型钙结合蛋白，它在神经内分泌细胞中表达。免疫组织化学研究使用鼠单克隆抗体和亲和纯化的兔多克隆抗分泌粒蛋白抗体，以及Northern印迹和Western印迹分析，揭示了一种神经元特异性的脑表达模式。在小脑皮质的篮状细胞和星状细胞、垂体前叶的分泌神经元以及额叶和顶叶新皮质的单个神经元中大量检测到分泌粒蛋白。在下丘脑和海马神经元中观察到显著的染色强度。使用新开发的夹心捕获ELISA，我们发现缺氧性神经元损伤患者的血清中存在分泌粒蛋白。在从32例因局灶性脑缺血而出现不同形式神经症状的患者中获得的血清中，分泌粒蛋白水平在3至{236} pg/ml之间，在梗死发生后的第2天和第3天观察到最高水平。3例表现出轻微、可逆性神经功能缺损的患者在检测时间点血清分泌粒蛋白水平无法检测到。在50份对照血清中，分泌粒蛋白低于我们ELISA的检测限。对14例代表性患者的分泌粒蛋白和已确立的神经生化标志物S-100B进行平行分析，结果相当。然而，S-100B水平更高，并且与分泌粒蛋白表现出不同的动力学。我们的数据展示了分泌粒蛋白的脑表达模式，并证明这种蛋白质可能代表一种与临床相关的血清标志物，可指示神经元损伤。
