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百草枯通过线粒体依赖途径诱导RAW264.7细胞凋亡。

Paraquat Induces Apoptosis through a Mitochondria-Dependent Pathway in RAW264.7 Cells.

作者信息

Jang Yeo Jin, Won Jong Hoon, Back Moon Jung, Fu Zhicheng, Jang Ji Min, Ha Hae Chan, Hong SeungBeom, Chang Minsun, Kim Dae Kyong

机构信息

Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.

出版信息

Biomol Ther (Seoul). 2015 Sep;23(5):407-13. doi: 10.4062/biomolther.2015.075. Epub 2015 Sep 1.

DOI:10.4062/biomolther.2015.075
PMID:26336579
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4556199/
Abstract

Paraquat dichloride (N,N-dimethyl-4-4'-bipiridinium, PQ) is an extremely toxic chemical that is widely used in herbicides. PQ generates reactive oxygen species (ROS) and causes multiple organ failure. In particular, PQ has been reported to be an immunotoxic agrochemical compound. PQ was shown to decrease the number of macrophages in rats and suppress monocyte phagocytic activity in mice. However, the effect of PQ on macrophage cell viability remains unclear. In this study, we evaluated the cytotoxic effect of PQ on the mouse macrophage cell line, RAW264.7 and its possible mechanism of action. RAW264.7 cells were treated with PQ (0, 75, and 150 μM), and cellular apoptosis, mitochondrial membrane potential (MMP), and intracellular ROS levels were determined. Morphological changes to the cell nucleus and cellular apoptosis were also evaluated by DAPI and Annexin V staining, respectively. In this study, PQ induced apoptotic cell death by dose-dependently decreasing MMP. Additionally, PQ increased the cleaved form of caspase-3, an apoptotic marker. In conclusion, PQ induces apoptosis in RAW264.7 cells through a ROS-mediated mitochondrial pathway. Thus, our study improves our knowledge of PQ-induced toxicity, and may give us a greater understanding of how PQ affects the immune system.

摘要

百草枯二氯化物（N，N-二甲基-4-4'-联吡啶鎓，PQ）是一种剧毒化学品，广泛用于除草剂。PQ会产生活性氧（ROS）并导致多器官功能衰竭。特别是，PQ已被报道为一种具有免疫毒性的农用化学化合物。研究表明，PQ会减少大鼠体内巨噬细胞的数量，并抑制小鼠单核细胞的吞噬活性。然而，PQ对巨噬细胞活力的影响仍不清楚。在本研究中，我们评估了PQ对小鼠巨噬细胞系RAW264.7的细胞毒性作用及其可能的作用机制。用PQ（0、75和150μM）处理RAW264.7细胞，并测定细胞凋亡、线粒体膜电位（MMP）和细胞内ROS水平。还分别通过DAPI和膜联蛋白V染色评估细胞核的形态变化和细胞凋亡。在本研究中，PQ通过剂量依赖性降低MMP诱导凋亡性细胞死亡。此外，PQ增加了凋亡标志物caspase-3的裂解形式。总之，PQ通过ROS介导的线粒体途径诱导RAW264.7细胞凋亡。因此，我们的研究增进了我们对PQ诱导毒性的了解，并可能使我们对PQ如何影响免疫系统有更深入的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a8d/4556199/48df2b0a2aee/bt-23-407f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a8d/4556199/36fe42d43e65/bt-23-407f1.jpg
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