Neurotrophic regulation of mouse muscle β‐amyloid protein precursor and α1‐antichymotrypsin as revealed by axotomy

Neurotrophic regulation of mouse muscle β‐amyloid protein precursor and α1‐antichymotrypsin as revealed by axotomy
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轴切术揭示小鼠肌肉 β-淀粉样蛋白前体和 α1-抗胰凝乳蛋白酶的神经营养调节

DOI:
10.1002/neu.480250505
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发表时间:
1994
期刊:
Journal of Neurobiology
影响因子:
--
通讯作者:
D. Hantaı̈
D. Hantaı̈
中科院分区:
--
文献类型:
--
作者:
M. Akaaboune;Jianxin Ma;B. Festoff;B. Greenberg;D. Hantaı̈

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含有Kunitz抑制剂的β-淀粉样前体蛋白(β APP)形式,也称为蛋白酶连接蛋白II(PNII)和α 1-抗胰凝乳蛋白酶(α 1-ACT),一种丝氨酸蛋白酶抑制剂,是许多组织中丝氨酸蛋白酶和抑制剂平衡的重要组分。在神经系统中,这种平衡可能在发育的不同阶段、损伤后和疾病状态下具有营养或生长因子活性。在目前的研究中,使用免疫细胞化学和蛋白质印迹与抗体对人类同源物,我们分析了是否去神经影响本地化的β APP和α 1-ACT在成年小鼠肌肉轴突切断术后。在小鼠肌肉中,抗人α 1-ACT抗体检测到60 kD的免疫反应带和抗人β APP抗体在92 kD的带在正常和失神经提取物。β APP存在于正常小鼠肌肉的神经肌肉接头和肌内神经中。在神经肌肉接头、神经束膜和内皮细胞表面也检测到α 1-ACT。轴突切断后,β APP和α 1-ACT同时从肌内神经消失。然而,在神经肌肉接头处,α 1-ACT下降得更快,β APP在消失前徘徊。由于α 1-ACT和β APP都存在于阿尔茨海默病大脑中的老年斑内,因此在去神经肌肉中用烟碱、胆碱能神经肌肉突触进行的这种实验可能有助于将实验集中在这种疾病中突触丧失以及斑块沉积的机制上。
Kunitz-inhibitor containing forms of the beta-amyloid precursor protein (beta APP), known also as protease nexin II (PNII), and alpha 1-antichymotrypsin (alpha 1-ACT), a serpin, are important components of the serine protease and inhibitor balance in many tissues. In the nervous system, this balance may have trophic or growth factor activity at different stages of development, after injury and in disease states. In the current study, using immunocytochemistry and Western blotting with antibodies against the human homologues, we analyzed whether denervation affected the localization of beta APP and alpha 1-ACT in adult mouse muscle following axotomy. In mouse muscle, anti-human alpha 1-ACT antibody detected a 60 kD immunoreactive band and anti-human beta APP antibody a band at 92 kD in both normal and denervated extracts. beta APP was present in normal mouse muscle at both neuromuscular junctions and within intramuscular nerves. alpha 1-ACT was also detected at neuromuscular junctions, on the perineurium and endothelial cell surfaces. Following axotomy, both beta APP and alpha 1-ACT disappeared from intramuscular nerves simultaneously. However, at the neuromuscular junction, alpha 1-ACT decreased more rapidly with beta APP lingering before disappearing. Since both alpha 1-ACT as well as beta APP are present within senile plaques in Alzheimer's disease brains such experiments with the nicotinic, cholinergic neuromuscular synapse in denervated muscle may help to focus experiments on the mechanism of synapse loss as well as plaque deposition in this disease.
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