CpG-Oligodeoxynucleotides Alleviate Tert-Butyl Hydroperoxide-Induced Macrophage Apoptosis by Regulating Mitochondrial Function and Suppressing ROS Production
CpG-Oligodeoxynucleotides Alleviate Tert-Butyl Hydroperoxide-Induced Macrophage Apoptosis by Regulating Mitochondrial Function and Suppressing ROS Production
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DOI：
10.1155/2020/1714352
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发表时间：
2020-05
影响因子：
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通讯作者：
Yibai Qu;Chunxiu Yang;Xueyang Li;Hai-hua Luo;Shan Li;Mengwei Niu;Peng Chen;Zhengzheng Yan
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文献类型：
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作者：
Yibai Qu;Chunxiu Yang;Xueyang Li;Hai-hua Luo;Shan Li;Mengwei Niu;Peng Chen;Zhengzheng Yan
氧化应激和线粒体功能障碍与疾病发病机制有关。含有 CpG 基序 (CpG ODN) 的寡脱氧核苷酸证明了免疫治疗应用的可能性。本工作的目的是通过利用免疫细胞中的氧化应激调节来探索 CpG ODN 的细胞保护功能的潜在机制。我们使用成像流式细胞术证明叔丁基过氧化氢 (t-BHP) 在 RAW264.7 细胞中诱导线粒体介导的细胞凋亡和 ROS 产生。用CpG ODN预处理后，凋亡细胞的百分比和ROS产生均显着降低。 t-BHP 诱导的线粒体膜电位 (MMP) 降低可被 CpG ODN 部分逆转。在 CpG ODN 存在下，t-BHP 诱导的凋亡相关蛋白（cleaved-caspase 3、cleaved-caspase 9、cleaved-PARP 和 bax）表达上调显着降低。此外，我们发现 CpG ODN 增强 ERK1/2 和 Akt 的磷酸化，从而抑制 ROS 的产生。总之，CpG ODN 在减轻 t-BHP 诱导的细胞凋亡中的保护作用取决于 ROS 的减少。
Oxidative stress and mitochondrial dysfunction are related to disease pathogenesis. Oligodeoxynucleotide containing CpG motifs (CpG ODN) demonstrate possibilities for immunotherapy applications. The aim of the present work is to explore the underlying mechanism of the cytoprotective function of CpG ODN by employing the oxidative stress modulation in immune cells. We used the imaging flow cytometry to demonstrate that tert-butyl hydroperoxide (t-BHP) induces mitochondrial-mediated apoptosis and ROS production in RAW264.7 cells. After pretreatment with CpG ODN, the percentage of apoptotic cells and ROS production was both markedly reduced. The decrease in mitochondrial membrane potential (MMP) induced by t-BHP was partially reversed by CpG ODN. The t-BHP induced upregulation of the expression of apoptosis-related proteins (cleaved-caspase 3, cleaved-caspase 9, cleaved-PARP, and bax) was notably decreased in the presence of CpG ODN. Furthermore, we found that CpG ODN enhanced phosphorylation of ERK1/2 and Akt to inhibit ROS production. In conclusion, the protective effect of CpG ODN in mitigation of t-BHP-induced apoptosis is dependent on the reduction of ROS.