Chitooligosaccharide-mediated neuroprotection is associated with modulation of Hsps expression and reduction of MAPK phosphorylation
Chitooligosaccharide-mediated neuroprotection is associated with modulation of Hsps expression and reduction of MAPK phosphorylation
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DOI：
10.1016/j.ijbiomac.2011.02.011
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发表时间：
2011-06-01
影响因子：
8.2
通讯作者：
Khodagholi, Fariba
中科院分区：
文献类型：
--
作者：
Joodi, Golsa;Ansari, Niloufar;Khodagholi, Fariba
越来越多的证据表明活性氧 (ROS) 诱导的氧化应激在神经退行性疾病（包括阿尔茨海默病）中的作用。在本研究中，我们旨在研究壳寡糖（COS）（一种抗氧化寡糖）对过氧化氢诱导的 NGF 分化大鼠嗜铬细胞瘤（PC12）细胞凋亡的可能保护作用。 COS 处理逆转了 H2O2 引起的细胞活力下降，这与细胞内 ROS 减少和胞质 Ca2+ 水平降低有关。此外，COS 还有助于 Bcl-2 的上调、Bax 蛋白的下调以及裂解的 Caspase-3 蛋白的减少。 COS处理稳定了细胞核中的Nrf2并增加了细胞内Hsp70的水平，同时下调了wHsp90的表达。此外，COS 可以抑制不同丝裂原激活蛋白激酶 (MAPK) 的磷酸化，而 MAPK 的异常磷酸化与 AD 有关。我们的研究结果表明，热休克反应和 MAPK 级联都与细胞存活有关，并且通过同时调节这两种途径，COS 可以成为治疗神经退行性疾病的有前途的药物。 (C) 2011 Elsevier B.V. 保留所有权利。
There is mounting evidence implicating the role of oxidative stress induced by reactive oxygen species (ROS) in neurodegenerative disease, including Alzheimer's disease. In this study we aimed to investigate the possible protective effect of chitooligosaccharide (COS), an antioxidant oligosaccharide, on hydrogen peroxide induced apoptosis in NGF-differentitated rat pheochromocytoma (PC12) cells. COS treatment reversed the decrease of cell viability induced by H2O2 and this was associated with diminished intracellular ROS and decreased level of cytosolic Ca2+. Additionally, COS contributed to up-regulation of Bcl-2, down regulation of Bax protein and reduction of cleaved Caspase-3 protein. COS treatment stabilized Nrf2 in nucleus and increased the Hsp70 level within cell while down-regulated wHsp90 expression. Moreover, COS could inhibit the phosphorylation of different mitogen activated protein kinases (MAPKs), whose aberrant phosphorylation has been implicated in AD. Our findings suggest that heat shock response and MAPK cascades are both involved in cell survival, and by concomitantly regulating both pathways, COS can be a promising agent in treating neurodegenerative diseases. (C) 2011 Elsevier B.V. All rights reserved.