Orexin-A protects SH-SY5Y cells against H(2)O(2)-induced oxidative damage via the PI3K/MEK(1/2)/ERK(1/2) signaling pathway.

Orexin-A protects SH-SY5Y cells against H(2)O(2)-induced oxidative damage via the PI3K/MEK(1/2)/ERK(1/2) signaling pathway.
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Orexin-A 通过 PI3K/MEK1/2/ERK1/2 信号通路保护 SH-SY5Y 细胞免受 H2O2 诱导的氧化损伤

DOI:
10.1177/2058738418785739
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发表时间:
2018-01
影响因子:
3.5
通讯作者:
Bai B
Bai B
中科院分区:
医学4区
文献类型:
--
作者:
Wang CM;Yang CQ;Cheng BH;Chen J;Bai B

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食欲素-A通过不同的信号通路对多种肿瘤细胞产生多种有效作用。然而,尚不清楚它是否对SH-SY 5 Y人神经母细胞瘤细胞具有神经保护作用。本研究探讨Orexin-A对过氧化氢(H2 O2)诱导的SH-SY 5 Y细胞氧化损伤的保护作用及其机制。H_2O_2处理可降低SH-SY 5 Y细胞的存活率,诱导细胞凋亡,并降低超氧化物歧化酶活性。Orexin-A减弱了这些作用,表明它保护SH-SY 5 Y细胞免受H2 O2诱导的氧化损伤。用Orexin-A预处理也减弱了H2 O2诱导的MEK 1/2和ERK 1/2磷酸化的增加。此外,在PI 3 K抑制剂LY 294002的存在下,食欲素-A的这些作用降低。最后,用LY 294002预处理消除了Orexin-A引起的H2 O2诱导的细胞活力降低和caspase-3/7活性增加的衰减。这些结果表明,PI 3 K/MEK 1/2/ERK 1/2信号通路参与Orexin-A对H2 O2诱导的SH-SY 5 Y细胞氧化损伤的神经保护作用。我们的研究结果提供了深入了解Orexin-A的神经保护作用及其机制,这将有助于治疗神经系统疾病。
Orexin-A elicits multiple potent effects on a variety of tumor cells via different signaling pathways. However, it is unknown whether it has a neuroprotective effect on SH-SY5Y human neuroblastoma cells. This study investigated the neuroprotective effect of Orexin-A against hydrogen peroxide (H2O2)-induced oxidative damage in SH-SY5Y cells and the underlying mechanism. H2O2 treatment decreased the viability of SH-SY5Y cells, induced apoptosis, and decreased superoxide dismutase activity. Orexin-A attenuated these effects, indicating that it protects SH-SY5Y cells against H2O2-induced oxidative damage. Pre-treatment with Orexin-A also attenuated H2O2-induced increases in phosphorylation of MEK1/2 and ERK1/2. Moreover, these effects of Orexin-A were reduced in the presence of the PI3K inhibitor LY294002. Finally, pre-treatment with LY294002 abrogated attenuation of the H2O2-induced decrease in cell viability and increase in caspase-3/7 activity by Orexin-A. These results show that the PI3K/MEK1/2/ERK1/2 signaling pathway is involved in the neuroprotective effects of Orexin-A against H2O2-induced oxidative damage in SH-SY5Y cells. Our findings provide insight into the neuroprotective effects of Orexin-A and the underlying mechanism, which will be useful for the treatment of nervous system diseases.
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