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垂体腺苷环化酶激活多肽抑制#beta#淀粉样蛋白对Neuro-2a细胞神经毒性作用的机制

桂兰润, 周岩, 张炳烈, 李文彬

北京军医学院病原室，北京100071 ； Department of Psychiatry , Yale University School of Medicine , Italy ；解放军总医院老年医学研究所，北京100853

摘要

通过MTT方法检测细胞活性，同时采用激光共聚焦显微镜技术检测细胞内游离钙离子的瞬时运动，研究了垂体腺普环化酶激活多肤( pituitary adenylate cyclase activating polypeptide 27 , PACAP27)通过调节细胞内钙对抗淀粉样蛋白邹25-35引起Neuro-2a细胞神经毒性作用的可能机制。结果表明，PACAP在一定浓度范围内(<0. 1umol/L)可提高Neuro-2a细胞增殖能力并对抗邹引起的神经毒性，此作用可以被PACAP受体竞争性拮抗剂
PACAP6-27所抑制。25 umol/ L邹使细胞内钙离子缓慢上升，并有一个较长时间的平台期。0.1 umol/L的PACAP细胞内钙离子迅速升高后下降，10 min后回到接近基线水平，伴有较长时间的不应期。用PACAP预处理细胞10min后邹引起细胞内钙的慢上升不再出现。推测，PACAP受体激活引起瞬时内向钙离子运动，而后伴随一个较长时间的不应期，可能是一个消除凋亡或阻止凋亡启动的保护机制。
关键词:0淀粉样蛋白;垂体腺普环化酶激活多肤(PACAP) ; Neuro-2a细胞;激光共聚焦显微镜;细胞内钙

关键词： #beta#淀粉样蛋白; 垂体腺苷环化酶激活多肽(PACAP); Neuro-2a细胞; 激光共聚焦显微镜; 细胞内钙

Pituitary adenyate cyclase activating polypeptide protects neura 2 a cells from #beta# amyloid protein cytotoxicity by modulating intracellular calcium

GUI Law Runi, ZHOU Yang, ZHANG Bingr Lie, Li Wenbin

Institute o f Microbiology, Beijing Military Medical College, Beijing 100071

Abstract

MTT analysis and intracellular calcium measurement by using confocal laser scanning microscopy were used to study the possible mechanism of protective effect of pituitary adenylate cyclase activating polypeptide 27(PACAP27) from p amyloid proteinA_(#beta#)induced neurotoxicity.The results
showed that treatment with PACAP(less than 0. 1 p mol/ L) increased the survival and reproductive aSility of neuro-2a cells and protected the neuro-2a cells from being injured byA_(#beta#)The protective effect of PACAP27 was reversed by the competitive PACAP receptor antagonist PACAP6-27 .An increase in intracellular calcium was observed when the cells were challenged withA_(#beta#)and PACAP·But the calcium increase induced byA_(#beta#)kept stable for a long time while PACAP caused a transient rise in intracellular calciu m.The intracellular calcium increase induced byA_(#beta#)was blocked by pretreatment with PACAP for 10 min.It is suggested that the neuroprotective effect of PACAP against neuronal damage induced byA_(#beta#) may result from its role in inhibiting the sustained rise in intracellular calcium.

Key words: p amyloid protein;pituitary adenylate cyclase ;;;

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引用本文：

桂兰润, 周岩, 张炳烈, 李文彬. 垂体腺苷环化酶激活多肽抑制#beta#淀粉样蛋白对Neuro-2a细胞神经毒性作用的机制[J]. 生理学报 2003; 55 (1): .

GUI Law Runi, ZHOU Yang, ZHANG Bingr Lie, Li Wenbin. Pituitary adenyate cyclase activating polypeptide protects neura 2 a cells from #beta# amyloid protein cytotoxicity by modulating intracellular calcium. Acta Physiol Sin 2003; 55 (1): (in Chinese with English abstract).