COPURIFICATION OF SP33-37 AND SCRAPIE AGENT FROM HAMSTER BRAIN PRIOR TO DETECTABLE HISTOPATHOLOGY AND CLINICAL-DISEASE
COPURIFICATION OF SP33-37 AND SCRAPIE AGENT FROM HAMSTER BRAIN PRIOR TO DETECTABLE HISTOPATHOLOGY AND CLINICAL-DISEASE
复制标题
DOI：
10.1099/0022-1317-72-12-2905
复制
发表时间：
1991-12-01
影响因子：
3.8
通讯作者：
BENDHEIM, PE
中科院分区：
文献类型：
--
作者：
BOLTON, DC;RUDELLI, RD;BENDHEIM, PE
进行研究以确定瘙痒病因子蛋白 Sp33-37 在大脑中的积累是否与瘙痒病因子的出现或病理相关。接种后每隔一周测量从仓鼠脑中分离的纯化级分 P5 中痒病剂和 Sp33-37 的浓度。接种后 1 天，P5 级分中的瘙痒剂浓度约为 10(-1) LD50/g 脑，并在第 77 天增加至 10(9.4) LD50/g。在第 21 天，当试剂滴度为 10(3.9) LD50/g 时，在 P5 中首次检测到 Sp33-37。 Sp33-37浓度与瘙痒症药物浓度一致增加，尽管蛋白质的表观增加率略低于该药物。疾病的组织病理学证据包括轻度空泡形成和神经胶质增生，在第 35 天首次出现，但直到接种后 49 至 56 天才明显。空泡和神经胶质增生增加，直到第 77 天实验终止。淀粉样斑块在第 56 天首次检测到，并在第 77 天广泛分布。这些动物在第 66 天首次发现临床疾病，平均在第 71 天发病。仅接种缓冲液的对照动物显示出一些轻度神经胶质增生，但其他方面均正常。在可检测到的（光学显微镜）病理学之前 14 天，用从大脑分离的痒病剂纯化了 Sp33-37，这一事实支持了这样的理论：Sp33-37 是痒病剂的主要结构成分，而不仅仅是病理学的产物。
Studies were conducted to determine whether accumulation of the scrapie agent protein Sp33-37 in brain correlated with the appearance of the scrapie agent or with pathology. The concentrations of the scrapie agent and Sp33-37 were measured in purified fraction P5 isolated from hamster brains at weekly intervals after inoculation. The scrapie agent concentration in fraction P5 was approximately 10(-1) LD50/g brain 1 day post-inoculation and increased to 10(9.4) LD50/g at day 77. Sp33-37 was first detected in P5 at day 21, when the agent titre was 10(3.9) LD50/g. Sp33-37 concentration increased in concert with the scrapie agent concentration, although the apparent rate of increase was somewhat lower for the protein than for the agent. The histopathological evidence of disease, consisting of mild vacuolation and gliosis, was first seen at 35 days, but was not conspicuous until 49 to 56 days postinoculation. Vacuolation and gliosis increased until termination of the experiment at day 77. Amyloid plaques were first detected at 56 days and were widespread at day 77. Clinical disease was first seen in these animals at day 66, with an average onset at day 71. Control animals inoculated with buffer alone showed some mild gliosis, but were otherwise normal. The fact that Sp33-37 purified with the scrapie agent isolated from brain 14 days prior to detectable (light microscopic) pathology supports the theory that Sp33-37 is the major structural component of the scrapie agent and not solely a product of the pathology.