Loganin protects against hydrogen peroxide-induced apoptosis by inhibiting phosphorylation of JNK, p38, and ERK 1/2 MAPKs in SH-SY5Y cells
Loganin protects against hydrogen peroxide-induced apoptosis by inhibiting phosphorylation of JNK, p38, and ERK 1/2 MAPKs in SH-SY5Y cells
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DOI：
10.1016/j.neuint.2011.01.012
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发表时间：
2011-03-01
影响因子：
4.2
通讯作者：
Jang, Choon-Gon
中科院分区：
文献类型：
--
作者：
Kwon, Seung-Hwan;Kim, Ji-Ah;Jang, Choon-Gon
我们研究了马钱素对过氧化氢 (H2O2) 诱导的 SH-SY5Y 细胞神经元毒性的保护作用的机制。通过用 H2O2 处理 SH-SY5Y 细胞，然后使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物 (MTT) 和乳酸脱氢酶 (LDH) 释放测定法测量 H2O2 诱导的细胞凋亡的减少，研究了马钱素的神经保护作用。 H2O2 暴露后，Hoechst 33258 染色表明大部分 SH-SY5Y 细胞出现核浓缩，同时活性氧 (ROS) 产生增加，细胞内线粒体膜电位 (MMP) 降低。马钱素可有效减弱 H2O2 诱导的所有上述表型。马钱素预处理显着增加细胞活力，减少H2O2诱导的LDH释放和ROS产生，并有效增加细胞内MMP。用马钱素预处理也显着降低了 H2O2 诱导的核凝结。 Western blot 数据显示，马钱素抑制 H2O2 诱导的裂解聚（ADP-核糖）聚合酶 (PARP) 和裂解 caspase-3 的上调，增加 H2O2 诱导的 Bcl-2/Bax 比值的下降，并减弱 H2O2 诱导的细胞色素 c 从线粒体到细胞质的释放。此外，用马钱素预处理可显着减弱 H2O2 诱导的 c-Jun N 末端激酶 (JNK)、p38 丝裂原激活蛋白激酶 (MAPK) 和细胞外信号调节激酶 1/2 (ERK 1/2) 的磷酸化。这些结果表明，马钱素对 H2O2 诱导的细胞凋亡的保护作用可能是由于抑制 JNK、p38 和 ERK 1/2 MAPK 的磷酸化而导致 Bcl-2/Bax 比率表达下降。马钱素的神经保护特性表明该化合物可能是治疗神经退行性疾病的潜在治疗剂。 Crown 版权所有 (C) 2011 由 Elsevier Ltd 出版。保留所有权利。
We investigated the mechanisms underlying the protective effects of loganin against hydrogen peroxide (H2O2)-induced neuronal toxicity in SH-SY5Y cells. The neuroprotective effect of loganin was investigated by treating SH-SY5Y cells with H2O2 and then measuring the reduction in H2O2-induced apoptosis using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays. Following H2O2 exposure, Hoechst 33258 staining indicated nuclear condensation in a large proportion of SH-SY5Y cells, along with an increase in reactive oxygen species (ROS) production and an intracellular decrease in mitochondria membrane potential (MMP). Loganin was effective in attenuating all the above-stated phenotypes induced by H2O2. Pretreatment with loganin significantly increased cell viability, reduced H2O2-induced LDH release and ROS production, and effectively increased intracellular MMP. Pretreatment with loganin also significantly decreased the nuclear condensation induced by H2O2. Western blot data revealed that loganin inhibited the H2O2-induced up-regulation of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase-3, increased the H2O2-induced decrease in the Bcl-2/Bax ratio, and attenuated the H2O2-induced release of cytochrome c from mitochondria to the cytosol. Furthermore, pretreatment with loganin significantly attenuated the H2O2-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase 1/2 (ERK 1/2). These results suggest that the protective effects of loganin against H2O2-induced apoptosis may be due to a decrease in the Bcl-2/Bax ratio expression due to the inhibition of the phosphorylation of JNK, p38, and ERK 1/2 MAPKs. Loganin's neuroprotective properties indicate that this compound may be a potential therapeutic agent for the treatment of neurodegenerative diseases. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.