Sonic Hedgehog Protects Cortical Neurons Against Oxidative Stress
Sonic Hedgehog Protects Cortical Neurons Against Oxidative Stress
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Sonic Hedgehog 保护皮质神经元免受氧化应激
DOI：
10.1007/s11064-010-0264-6
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发表时间：
2011-01-01
影响因子：
4.4
通讯作者：
Hu, Bo
中科院分区：
文献类型：
--
作者：
Dai, Ruo-Lian;Zhu, Sheng-Yin;Hu, Bo
氧化应激是神经退行性疾病和缺血最重要的病理机制之一。最近的研究表明，声波刺猬（SHH）信号通路与这些疾病有关，但其潜在机制仍然难以捉摸。在这里，我们报告说，在暴露于过氧化氢（H2O2）后，原代培养的皮层神经元中的 SHH 通路被激活。 H2O2处理降低了神经元的细胞活力，而内源性SHH信号传导的抑制则加剧了其神经毒性。 SHH 信号的激活可以保护神经元免受 H2O2 诱导的细胞凋亡并增加细胞活力，而通过阻断 SHH 信号可以部分逆转这些作用。外源性 SHH 增加 H2O2 处理的神经元中超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GSH-PX) 的活性，并减少丙二醛 (MDA) 的产生。它还促进抗凋亡基因Bcl-2的表达并抑制促凋亡基因Bax的表达。 SHH 信号的激活上调神经营养因子血管内皮生长因子 (VEGF) 和脑源性神经营养因子 (BDNF)。 SHH 预处理抑制了 H2O2 诱导的 ERK（细胞外信号调节激酶）信号的激活。我们的研究结果表明，SHH 信号的激活可以保护皮质神经元免受氧化应激，并表明 SHH 在脑缺血和神经退行性疾病的临床治疗中具有潜在作用。
Oxidative stress is one of the most important pathological mechanisms in neurodegenerative diseases and ischemia. Recent studies have indicated that the sonic hedgehog (SHH) signaling pathway is involved in these diseases, but the underlying mechanisms remains elusive. Here we report that the SHH pathway was activated in primary cultured cortical neurons after exposure to hydrogen peroxide (H2O2). H2O2treatment decreased the cell viability of neurons, and inhibition of endogenous SHH signaling exacerbated its neurotoxicity. Activation of SHH signaling protected neurons from H2O2-induced apoptosis and increased the cell viability while those effects were partially reversed by blocking SHH signals. Exogenous SHH increased the activities of Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-PX) in H2O2-treated neurons and decreased production of Malondialdehyde (MDA). It also promoted expression of the anti-apoptotic gene Bcl-2 and inhibited expression of pro-apoptotic gene Bax. Activation of SHH signals upregulated both Neurotrophic factors vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). Pretreatment with SHH inhibited the activation of ERK (extracellular signal-regulated kinases) signals induced by H2O2. Our findings demonstrate that activation of SHH signaling protects cortical neurons against oxidative stress and suggest a potential role of SHH for the clinic treatments of brain ischemia and neurodegenerative disorders.