Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation.
Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation.
复制标题
天麻素通过 p38 MAPK 磷酸化诱导 HO-1 和 Nrf2 上调，减轻 H2O2 诱导的小鼠肝窦内皮细胞氧化应激
DOI：
10.1590/1414-431x20187439
复制
发表时间：
2018-08-16
期刊：
影响因子：
--
通讯作者：
Zeng Z
中科院分区：
文献类型：
--
作者：
Zhang H;Yuan B;Huang H;Qu S;Yang S;Zeng Z
核因子-红细胞相关因子2 （Nrf2）参与多种解毒和抗氧化防御过程。nrf2介导的血红素氧化酶-1 （HO-1）表达在抗氧化应激中起关键作用。天麻素（GSTD）是一种著名的活性化合物，从天麻根中分离出来，是一种古老的中药植物。本实验旨在探讨GSTD是否能减轻h2o2诱导的小鼠肝窦内皮细胞（LSECs）氧化应激。在暴露于1 mM H2O2的LSECs中，GSTD（1、10或50µM）处理的细胞活力高于未处理的对照组。与未处理的细胞相比，处理后的细胞保持较高的Bcl2/Bax比率，抑制caspase-9的表达，减少细胞凋亡。GSTD通过减少细胞内活性氧和丙二醛的产生，对h2o2诱导的氧化损伤具有保护作用。GSTD可协同上调HO-1和Nrf2的表达。在h2o2暴露的LSECs中，10µM原卟啉锌对HO-1的抑制作用对GSTD处理的细胞活力和丙二醛还原的保护作用较小。此外，暴露于H2O2的LSECs中磷酸化的p38被GSTD升高。在1或10µM GSTD处理后，SB203580抑制p38磷酸化并没有诱导Nrf2和HO-1的表达，并且对h2o2暴露LSECs细胞活力和丙二醛还原的保护作用降低。结果表明，gstd诱导的HO-1和Nrf2表达参与了LSECs免受h2o2诱导的氧化损伤的保护，这可能与p38磷酸化有关。
Nuclear factor erythroid-related factor 2 (Nrf2) has been implicated in several detoxifying and antioxidant defense processes. Nrf2-mediated heme oxygenase-1 (HO-1) expression was demonstrated to play a key role against oxidative stress. Gastrodin (GSTD) is a well-known active compound isolated from the roots of Rhizoma gastrodiae, a plant used in ancient Chinese traditional medicine. The aim of this work was to investigate whether GSTD could alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells (LSECs). In LSECs exposed to 1 mM H2O2, treatment with GSTD (1, 10, or 50 µM) resulted in higher cell viability than the untreated control. Treated cells maintained a higher Bcl2/Bax ratio and suppressed caspase-9 expression compared with untreated cells, reducing cell apoptosis. GSTD was protective for H2O2-induced oxidative injury by reducing the generation of intracellular reactive oxygen species and malondialdehyde. HO-1 and Nrf2 expressions were synergistically upregulated by GSTD. Inhibition of HO-1 by 10 µM zinc protoporphyrin resulted in less protective effects on cell viability and malondialdehyde reduction by GSTD treatment in H2O2-exposed LSECs. Additionally, phosphorylated p38 in LSECs exposed to H2O2 was elevated by GSTD. Inhibition of p38 phosphorylation by SB203580 did not induce Nrf2 and HO-1 expression after 1 or 10 µM GSTD treatment and the protective effect on cell viability and malondialdehyde reduction in H2O2-exposed LSECs was reduced. The data conclusively demonstrated that GSTD-induced HO-1 and Nrf2 expression is involved in protection of LSECs from H2O2-induced oxidative injury, which may be regulated by p38 phosphorylation.