Characterization of dopamine-depleting activity of Nocardia asteroides strain GUH-2 culture filtrate on PC12 cells
Characterization of dopamine-depleting activity of Nocardia asteroides strain GUH-2 culture filtrate on PC12 cells
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DOI：
10.1016/j.micpath.2004.05.001
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发表时间：
2004-08-01
影响因子：
3.8
通讯作者：
LeWitt, PA
中科院分区：
文献类型：
--
作者：
Loeffler, DA;Camp, DM;LeWitt, PA
用革兰氏阳性细菌星状诺卡氏菌（菌株GUH-2）实验性感染BALB/c小鼠导致终身运动异常，包括头部摇晃和被尾巴抓住时旋转。用多巴胺的前体左旋多巴治疗可以暂时抑制摇头，这表明多巴胺能神经传递的异常可能与这些运动异常有关。从N. asteroides培养物在大鼠嗜铬细胞瘤PC 12细胞中诱导>70%的多巴胺消耗，表明诺卡氏菌对多巴胺神经元的作用可能部分来自分泌因子。在本研究中，这种多巴胺消耗活动的性质进行了检查。N.星状体培养物滤液耐热（100 ℃ × 30分钟）、蛋白酶和氯仿提取，并且以低分子量（< 3 kDa）级分存在。GUH-2滤液增加细胞乳酸脱氢酶释放只有2%，诱导凋亡的形态，只有11%的PC 12细胞，表明多巴胺消耗活性不是由于细胞损伤或诱导凋亡。这些结果表明，N.小行星可能是其多巴胺消耗效应的原因。(C)2004爱思唯尔有限公司保留所有权利。
Experimental infection of BALB/c mice with the Gram-positive bacterium Nocardia asteroides (strain GUH-2) results in life-long movement abnormalities including head shaking and spinning when held by the tail. The head shaking is temporarily inhibited by treatment with dopamine's precursor levodopa, suggesting that abnormalities in dopaminergic neurotransmission may be involved in these movement abnormalities. Cell-free filtrates from N. asteroides cultures induce >70% dopamine depletion in rat pheochromocytoma PC12 cells, suggesting that Nocardia's effects on dopamine neurons may result in part from secreted factors. The nature of this dopamine-depleting activity was examined in the present study. Dopamine-depleting activity in N. asteroides culture filtrate was resistant to heat (100 degreesC X 30 min), proteases, and chloroform extraction, and was present in a low molecular mass (< 3 kDa) fraction. It was partially inhibited by decreasing (to 4.0) or increasing (to 10.0) the filtrate pH. GUH-2 filtrate increased cellular lactate dehydrogenase release by only 2%, and induced apoptotic morphology in only 11% of PC12 cells, suggesting that dopamine-depleting activity was not due to either cell injury or induction of apoptosis. These results suggest that a protease-resistant, low molecular mass substance secreted by N. asteroides may be responsible for its dopamine-depleting effects. (C) 2004 Elsevier Ltd. All rights reserved.