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蛇葡萄素通过 ERK 和 Akt 信号通路及血红素加氧酶-1 的上调抑制 H₂O₂诱导的细胞凋亡。

Ampelopsin inhibits H₂O₂-induced apoptosis by ERK and Akt signaling pathways and up-regulation of heme oxygenase-1.

机构信息

College of Health Science, Wu Han Institute of Physical Education, PR China.

出版信息

Phytother Res. 2012 Jul;26(7):988-94. doi: 10.1002/ptr.3671. Epub 2011 Dec 6.

DOI:10.1002/ptr.3671
PMID:22144097
Abstract

Oxidative stress plays an important role in neurodegenerative disorders. Ampelopsin, a flavonoid abundant in Rattan tea (Ampelopsis grossedentata), is a potent antioxidant and its neuroprotective effect against H₂O₂-induced apoptosis in PC12 cells is investigated here for the first time. It was found that treatment of cells with ampelopsin for 1 h significantly reduced the loss of vitality, LDH release and apoptosis and inhibited the formation of reactive oxygen species (ROS). Ampelopsin was able to prevent the activation of p38 induced by H₂O₂. In addition, up-regulation of heme oxygenase-1 (HO-1) expression by ampelopsin was shown to be both dose- and time-dependent. Mechanically, HO-1 expression induced by ampelopsin was found to be due to activation of the ERK and Akt signaling pathways, because it was almost completely blocked by the specific inhibitors of ERK and Akt. These results suggest that ampelopsin increases cellular antioxidant defense through activation of the ERK and Akt signaling pathways, which induces HO-1 expression and thereby protects PC12 cells from H₂O₂-induced apoptosis.

摘要

氧化应激在神经退行性疾病中起着重要作用。二氢杨梅素是虎杖(Ampelopsis grossedentata)中丰富的一种黄酮类化合物,具有很强的抗氧化作用,本研究首次探讨了其对 H₂O₂诱导的 PC12 细胞凋亡的神经保护作用。结果发现,用二氢杨梅素处理细胞 1 h 可显著减少活力损失、LDH 释放和细胞凋亡,并抑制活性氧(ROS)的形成。二氢杨梅素能阻止 H₂O₂诱导的 p38 的激活。此外,二氢杨梅素对血红素加氧酶-1(HO-1)表达的上调呈剂量和时间依赖性。从机制上讲,发现二氢杨梅素诱导的 HO-1 表达是由于 ERK 和 Akt 信号通路的激活,因为它几乎完全被 ERK 和 Akt 的特异性抑制剂阻断。这些结果表明,二氢杨梅素通过激活 ERK 和 Akt 信号通路增加细胞抗氧化防御,从而诱导 HO-1 表达,从而保护 PC12 细胞免受 H₂O₂诱导的凋亡。

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