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缺陷神经肽处理和缺血性脑损伤:大脑缺血时蛋白转化酶2及其底物神经肽的研究 |
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Defective neuropeptide processing and ischemic brain injury: A study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains |
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Zhan S., Zhao H., J White A., Minami M., Pignataro G., Yang T., Zhu X., Lan J., Xiong Z., Steiner D.F., Simon R.P., Zhou A. 2009/5/29 18:38:56 |
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Journal of Cerebral Blood Flow and Metabolism, 2009, Volume 29, Issue 4
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Using a focal cerebral ischemia model in rats, brain ischemia-induced changes in expression levels of mRNA and protein, and activities of proprotein convertase 2 (PC2) in the cortex were examined. In situ hybridization analyses revealed a transient upregulation of the mRNA level for PC2 at an early reperfusion hour, at which the level of PC2 protein was also high as determined by immunocytochemistry and western blotting. When enzymatic activities of PC2 were analyzed using a synthetic substrate, a significant decrease was observed at early reperfusion hours at which levels of PC2 protein were still high. Also decreased at these reperfusion hours were tissue levels of dynorphin-A(1-8) (DYN-A(1-8)), a PC2 substrate, as determined by radioimmunoassay. Further examination of PC2 protein biosynthesis by metabolic labeling in cultured neuronal cells showed that in ischemic cells, the proteolytic processing of PC2 was greatly attenuated. Finally, in mice, an intracerebroventricular administration of synthetic DYN-A(1-8) significantly reduced the extent of ischemic brain injury. In mice those lack an active PC2, exacerbated brain injury was observed after an otherwise non-lethal focal ischemia. We conclude that brain ischemia attenuates PC2 and PC2-mediated neuropeptide processing. This attenuation may play a role in the pathology of ischemic brain injury. © 2009 ISCBFM All rights reserved. |
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Correspondence Address: Zhou, A.; Robert S. Dow Neurobiology Laboratories, Legacy Clinic Research and Technology Center, 1225 NE 2nd Avenue, Portland, OR 97232, United States; email: azhou@downeurobiology.org |
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疾病资源中心
摘自:《西氏内科学》,第23版
患者女性,21岁,因干咳、间歇性气促2个月到急诊科就诊。开始症状为上呼吸道感染引起的鼻塞、流涕和咳嗽。医生检查后开了抗生素。服药后鼻部症状缓解,但仍有轻微干咳和呼吸困难。其他症状包括疲劳和焦虑。否认发热、体重减轻、胸痛、端坐呼吸、气喘、鼻后滴漏、胃灼热以及神经系统症状。
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