HO-1 Is Essential for Tetrahydroxystilbene Glucoside Mediated Mitochondrial Biogenesis and Anti-Inflammation Process in LPS-Treated RAW264.7 Macrophages.
HO-1 Is Essential for Tetrahydroxystilbene Glucoside Mediated Mitochondrial Biogenesis and Anti-Inflammation Process in LPS-Treated RAW264.7 Macrophages.
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HO-1 对于 LPS 处理的 RAW264.7 巨噬细胞中四羟基二苯乙烯葡萄糖苷介导的线粒体生物发生和抗炎过程至关重要
DOI：
10.1155/2017/1818575
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发表时间：
2017
影响因子：
--
通讯作者：
Hai C
中科院分区：
文献类型：
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作者：
Yu W;Zhang X;Wu H;Zhou Q;Wang Z;Liu R;Liu J;Wang X;Hai C
2，3，5，4 ′-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（2，3，5，4 ′-Tetrahydroxystilbene-2-O-β-D-glucoside，TSG）是何首乌中提取的一种重要单体，具有预防多种炎症相关慢性疾病的作用。然而，TSG诱导抗炎作用的机制尚不清楚。血红素加氧酶-1（HO-1）作为一种诱导型抗氧化酶，在保护哺乳动物细胞免受不良刺激中起着重要作用。在这里，我们发现，TSG处理强烈诱导HO-1的表达在NRF 2依赖的方式。同时，TSG通过上调线粒体生物合成激活因子（PGC-1α、NRF 1和TFAM）以及线粒体复合物IV增加线粒体质量。此外，TSG还能抑制脂多糖（LPS）介导的RAW264.7细胞活化和分泌促炎细胞因子，包括白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）。锌原卟啉（ZnPP）是一种HO-1活性的选择性抑制剂，能够减弱TSG介导的线粒体生物合成和抗炎过程。最后，我们观察到LPS引起线粒体DNA明显缺失和ATP缺乏，这表明线粒体严重受损。TSG通过激活线粒体生物合成来恢复LPS诱导的线粒体功能障碍。ZnPP处理显著逆转TSG对LPS刺激的巨噬细胞线粒体损伤和氧化应激的抑制作用。总之，这些发现表明，TSG主要通过激活HO-1来增强线粒体生物发生和功能。TSG可作为一种潜在的治疗炎症性疾病的药物。
2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an important monomer extracted from Polygonum multiflorum, can prevent a number of inflammation associated chronic diseases. However, the mechanism involved in TSG inducing anti-inflammatory role remains unclear. As an inducible antioxidant enzyme, Heme oxygenase-1 (HO-1), is crucial for protecting the mammalian cells against adverse stimuli. Here, we found that the TSG treatment strongly induces the expression of HO-1 in an NRF2-depended manner. Meanwhile, TSG increased the mitochondrial mass through upregulation of the mitochondrial biogenesis activators (PGC-1α, NRF1, and TFAM) as well as the mitochondrial complex IV. Furthermore, TSG attenuated Lipopolysaccharide (LPS) mediated RAW264.7 cells activation and secretion of proinflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Zinc Protoporphyrin (ZnPP), a selective inhibitor of HO-1 activity, was able to attenuate TSG mediated mitochondrial biogenesis and anti-inflammatory process. Finally, we observed that LPS induced obvious mtDNA depletion and ATP deficiency, which indicated a severe damage of mitochondria. TSG restored the LPS induced mitochondrial dysfunction via activation of the mitochondrial biogenesis. ZnPP treatment markedly reversed the inhibitory effects of TSG on mitochondrial damage and oxidative stress in LPS stimulated macrophages. Taken together, these findings suggest that TSG enhances mitochondrial biogenesis and function mainly via activation the HO-1. TSG can be developed as a potential drug for treatment of inflammatory diseases.