Nrf2 Mediates the Anti-apoptotic and Anti-inflammatory Effects Induced by Gastrodin in Hydrogen Peroxide-Treated SH-SY5Y Cells
Nrf2 Mediates the Anti-apoptotic and Anti-inflammatory Effects Induced by Gastrodin in Hydrogen Peroxide-Treated SH-SY5Y Cells
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DOI：
10.1007/s12031-019-01339-3
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发表时间：
2019-09-01
影响因子：
3.1
通讯作者：
Furstenau, Cristina Ribas
中科院分区：
文献类型：
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作者：
de Oliveira, Marcos Roberto;Brasil, Flavia Bittencourt;Furstenau, Cristina Ribas
氧化还原障碍，炎症和细胞死亡率增加是神经退行性过程中的核心参与者。在这种情况下，转录因子核因子核因子2相关因子2（NRF2）的激活已被视为一种有趣的策略，以减少氧化还原功能障碍和神经炎症对细胞命运的影响。有证据表明，大脑中天然产物引起的益处可能是由于这些药物在上调NRF2方面的能力。胃生素（气体）诱导脑细胞中的抗氧化剂，抗炎和抗凋亡作用。但是，这种效果的基础机制尚不清楚。因此，我们在这里调查了气体是否会影响暴露于过氧化氢的人神经母细胞瘤细胞系（SH-SY5Y）中的凋亡和炎症（H2O2）。在30分钟内将1-25 mu m处的气体施加到细胞中，然后在300 mu m的H2O2挑战24小时内进行挑战。气体通过调节Bcl-2和Bax的水平来阻止固有凋亡途径的激活，从而导致细胞色素C释放到细胞质。气体还阻止了促凋亡酶caspase-9和caspase-3的激活。因此，在H2O2处理的SH-SY5Y细胞中，气体废除了聚（ADP-核糖）聚合酶（PARP）裂解和DNA片段化。此外，气体降低了白介素-1β（IL-1β）和肿瘤坏死因子-Alpha（TNF-Alpha）的水平以及H2O2处理的细胞中核因子-KAPPA B的活性。通过小干扰RNA（siRNA）对NRF2进行沉默，抑制了气体诱导的细胞保护作用。因此，气体通过涉及SH-SY5Y细胞中NRF2的机制引起抗凋亡和抗炎作用。
Redox impairment, inflammation, and increased rates of cell death are central players during neurodegeneration. In that context, activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been viewed as an interesting strategy in order to reduce the impact of redox dysfunction and neuroinflammation on cell fate. There is evidence indicating that the benefits caused by natural products in the brain may be due to the ability of these agents in upregulating Nrf2. Gastrodin (GAS) induces anti-oxidant, anti-inflammatory, and anti-apoptotic actions in brain cells. Nonetheless, the mechanisms underlying such effects are not clear yet. Therefore, we investigated here whether GAS would affect apoptosis and inflammation in the human neuroblastoma cell line (SH-SY5Y) exposed to hydrogen peroxide (H2O2). GAS at 1-25 mu M was administrated to the cells during 30 min before a challenge with H2O2 at 300 mu M for additional 24 h. GAS prevented the activation of the intrinsic apoptotic pathway by modulating the levels of Bcl-2 and Bax, causing a decrease in the release of cytochrome c to the cytosol. GAS also prevented the activation of the pro-apoptotic enzymes caspase-9 and caspase-3. Consequently, GAS abrogated poly (ADP-ribose) polymerase (PARP) cleavage and DNA fragmentation in the H2O2-treated SH-SY5Y cells. Moreover, GAS reduced the levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) and the activity of nuclear factor-kappa B in H2O2-treated cells. Silencing of Nrf2 by small interfering RNA (siRNA) suppressed the GAS-induced cytoprotection. Thus, GAS elicited anti-apoptotic and anti-inflammatory effects by a mechanism involving Nrf2 in SH-SY5Y cells.