Biomol Ther.  2015 Sep;23(5):407-413. 10.4062/biomolther.2015.075.

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

• Jang YJ
• Won JH
• Back MJ
• Fu Z
• Jang JM
• Ha HC
• Hong S
• Chang M
• Kim DK

• KMID: 2380288
• DOI: http://doi.org/10.4062/biomolther.2015.075

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 muM), 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.

Keyword

Paraquat; RAW264.7 cells; Apoptosis; Mitochondria; ROS

MeSH Terms

Animals
Annexin A5
Apoptosis*
Caspase 3
Cell Death
Cell Line
Cell Nucleus
Cell Survival
Herbicides
Immune System
Macrophages
Membrane Potential, Mitochondrial
Mice
Mitochondria
Monocytes
Multiple Organ Failure
Paraquat*
Rats
Reactive Oxygen Species
Annexin A5
Caspase 3
Herbicides
Paraquat
Reactive Oxygen Species