Department of Chemistry/ICET, Federal University of Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, Cuiaba, MT, 78060-900, Brazil.
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Mol Neurobiol. 2018 Feb;55(2):989-1003. doi: 10.1007/s12035-016-0380-7. Epub 2017 Jan 13.
Mitochondria are susceptible to redox impairment, which has been associated with neurodegeneration. These organelles are both a source and target of reactive species. In that context, there is increasing interest in finding natural compounds that modulate mitochondrial function and mitochondria-related signaling in order to prevent or to treat diseases involving mitochondrial impairment. Herein, we investigated whether and how pinocembrin (PB) would prevent mitochondrial dysfunction elicited by the exposure of human neuroblastoma SH-SY5Y cells to hydrogen peroxide (HO). PB (25 μM) was administrated for 4 h before HO treatment (300 μM for 24 h). PB prevented HO-induced loss of cell viability mitochondrial depolarization in SH-SY5Y cells. PB also attenuated redox impairment in mitochondrial membranes. The production of superoxide anion radical (O) and nitric oxide (NO) was alleviated by PB in cells exposed to HO. PB suppressed the HO-induced inhibition of the tricarboxylic acid (TCA) cycle enzymes aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. Furthermore, PB induced anti-inflammatory effects by abolishing the HO-dependent activation of the nuclear factor-κB (NF-κB) and upregulation of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The PB-induced antioxidant and anti-inflammatory effects are dependent on the heme oxygenate-1 (HO-1) enzyme and on the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), since HO-1 inhibition (with 0.5 μM ZnPP IX) or Nrf2 silencing (with small interfering RNA (siRNA)) abolished the effects of PB. Overall, PB afforded cytoprotection by the Nrf2/HO-1 axis in HO-treated SH-SY5Y cells.
线粒体易受氧化还原损伤影响，这与神经退行性变有关。这些细胞器既是活性物质的来源又是其靶点。在这种情况下，人们越来越有兴趣寻找调节线粒体功能和与线粒体相关信号的天然化合物，以预防或治疗涉及线粒体损伤的疾病。在此，我们研究了白杨素（PB）是否以及如何预防人类神经母细胞瘤 SH-SY5Y 细胞暴露于过氧化氢（HO）时引起的线粒体功能障碍。PB（25μM）在 HO 处理前（300μM 处理 24 小时）给药 4 小时。PB 可防止 HO 诱导的 SH-SY5Y 细胞活力丧失和线粒体去极化。PB 还减轻了线粒体膜的氧化还原损伤。在暴露于 HO 的细胞中，超氧阴离子自由基（O）和一氧化氮（NO）的产生被 PB 减轻。PB 抑制 HO 诱导的三羧酸（TCA）循环酶顺乌头酸酶、α-酮戊二酸脱氢酶和琥珀酸脱氢酶的抑制。此外，PB 通过消除 HO 依赖性核因子-κB（NF-κB）激活和白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的上调来发挥抗炎作用。PB 诱导的抗氧化和抗炎作用依赖于血红素加氧酶-1（HO-1）酶和转录因子红细胞生成 2 相关因子 2（Nrf2）的激活，因为 HO-1 抑制（用 0.5μM ZnPP IX）或 Nrf2 沉默（用小干扰 RNA（siRNA））消除了 PB 的作用。总的来说，PB 通过 Nrf2/HO-1 轴在 HO 处理的 SH-SY5Y 细胞中提供细胞保护。
