Humanin rescues cortical neurons from prion-peptide-induced apoptosis
Humanin rescues cortical neurons from prion-peptide-induced apoptosis
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DOI：
10.1016/j.mcn.2003.09.017
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发表时间：
2004-01-01
影响因子：
3.5
通讯作者：
Pillot, T
中科院分区：
文献类型：
--
作者：
Sponne, I;Fifre, A;Pillot, T
最近，我们证实了一种可溶性的寡聚型PrP多肽，推测为PrP的118-135跨膜结构域，具有膜融合特性，在体外和体内都能诱导细胞凋亡。最近发现的一种救援因子人素(HN)被证明可以保护神经细胞免受与人类神经退行性疾病有关的各种伤害。因此，我们提出了HN是否可能调节可溶性PrP(118-135)片段诱导的细胞凋亡的问题。我们发现，大鼠皮质神经元与10um HN孵育，在抑制凋亡事件的同时，可以防止可溶性PrP(118-135)片段诱导的细胞死亡。一种称为HNG的HN变体在大脑皮层神经元中显示出500倍的保护活性，而HNA变体则没有显示出保护作用。HN和HNG多肽的作用不需要与PrP(118-135)片段预先孵育，这强烈表明这些多肽独立于与PrP(118-135)片段的直接相互作用而拯救细胞。相反，与先前的研究一致，HN对纤维PrP(106-126)肽诱导的细胞死亡没有影响。这种对PrP(118-135)片段诱导的神经元死亡的保护作用强烈地表明PrP(118-135)和PrP(106-126)肽可能触发不同的途径导致神经元凋亡。(C)2003 Elsevier Inc.保留所有权利。
We recently demonstrated that a soluble oligomeric prion peptide, the putative 118-135 transmembrane domain of prion protein (PrP), exhibited membrane fusogenic properties and induced apoptotic cell death both in vitro and in vivo. A recently discovered rescue factor humanin (HN) was shown to protect neuronal cells from various insults involved in human neurodegenerative diseases. We thus addressed the question of whether HN might modulate the apoptosis induced by the soluble PrP(118-135) fragment. We found that the incubation of rat cortical neurons with 10 muM HN prevented soluble PrP(118-135) fragment-induced cell death concomitantly with inhibition of apoptotic events. An HN variant, termed HNG, exhibited a 500-fold increase in the protective activity in cortical neurons, whereas the HNA variant displayed no protective effect. The effects of HN and HNG peptides did not require a preincubation with the PrP(118-135) fragment, strongly suggesting that these peptides rescue cells independently of a direct interaction with the prion peptide. By contrast, and in agreement with a previous study, HN had no effect on the fibrillar PrP(106-126) peptide-induced cell death. This protective effect for neurons from PrP(118-135) fragment-induced cell death strongly suggests that PrP(118-135) and PrP(106-126) peptides may trigger different pathways leading to neuronal apoptosis. (C) 2003 Elsevier Inc. All rights reserved.