Paraquat Induces Apoptosis through a Mitochondria-Dependent Pathway in RAW264.7 Cells.
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.
Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Yeo Jin
YJ
Jang
Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Jong Hoon
JH
Won
Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Moon Jung
MJ
Back
Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Zhicheng
Z
Fu
Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Ji Min
JM
Jang
Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Hae Chan
HC
Ha
Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
SeungBeom
S
Hong
Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Minsun
M
Chang
Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Dae Kyong
DK
Kim
Apoptosis; Mitochondria; Paraquat; RAW264.7 cells; ROS