Characterization of α1-antitrypsin as a heme oxygenase-1 suppressor in Alzheimer plasma
Characterization of α1-antitrypsin as a heme oxygenase-1 suppressor in Alzheimer plasma
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DOI：
10.1016/j.nbd.2006.06.009
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发表时间：
2006-10-01
影响因子：
6.1
通讯作者：
Schipper, Hyman M.
中科院分区：
文献类型：
--
作者：
Maes, Olivier C.;Kravitz, Steven;Schipper, Hyman M.
在阿尔茨海默病(AD)患者的血液、脑脊液(CSF)和脉络丛中，血红素氧合酶-1(HO-1)的mRNA和蛋白水平降低。在此，通过星形胶质细胞生物测定、生化技术和免疫荧光共聚焦显微镜证实了血红素加氧酶-1抑制因子(HOS)的存在。我们报告说，与健康的老年人和神经对照组相比，AD患者的血浆HOS活性显著增强。HOS因子被确定为一种50-100 kDa不稳定的肝素结合糖蛋白，与抗氧化剂摄入量、血浆总抗氧化能力、循环皮质醇水平或载脂蛋白E epsilon 4携带者状态无关。外源性α(1)-抗胰蛋白酶重现HOS生物活性。AD患者血浆α(1)-抗胰蛋白酶水平显著升高，并与HOS活性和MMSE评分呈正相关。α(1)-抗胰蛋白酶免疫耗竭可降低AD患者血浆HOS活性。在AD脑内，α(1)-抗胰蛋白酶免疫反应增强，并与HO-1共分布。α(1)-抗胰蛋白酶的HOS活性可能抑制HO-1依赖的脑铁稳态紊乱，并解释AD外周组织HO-1表达减少的原因。(C)2006 Elsevier Inc.保留所有权利。
Heme oxygenase-1 (HO-1) mRNA and protein levels are diminished in Alzheimer disease (AD) blood, cerebrospinal fluid (CSF) and choroid plexus. Herein, the presence of a heme oxygenase-1 suppressor (HOS) factor was ascertained by astroglial bioassay, biochemical techniques and immunofluorescence confocal microscopy. We report significantly augmented plasma HOS activity in AD patients relative to healthy elderly and neurological controls. The HOS factor was determined to be a 50-100 kDa beat-labile, heparin-binding glycoprotein that is unrelated to antioxidant ingestion, plasma total antioxidant capacity, circulating cortisol levels or apolipoprotein E epsilon 4 carrier status. HOS bioactivity was recapitulated by exogenous alpha(1)-antitrypsin. alpha(1)-antitrypsin levels were significantly increased in AD plasma and correlated with HOS activity and MMSE scores. alpha(1)-antitrypsin immunodepletion attenuated HOS activity of AD plasma. In AD brain, alpha(1)-antitrypsin immunoreactivity was augmented and co-distributed with HO-1. HOS activity of alpha(1)-antitrypsin may curtail HO-1-dependent derangement of cerebral iron homeostasis and account for diminished HO-1 expression in AD peripheral tissues. (c) 2006 Elsevier Inc. All rights reserved.