Paraquat Induces Apoptosis through a Mitochondria-Dependent Pathway in RAW264.7 Cells.
10.4062/biomolther.2015.075
- Author:
Yeo Jin JANG
1
;
Jong Hoon WON
;
Moon Jung BACK
;
Zhicheng FU
;
Ji Min JANG
;
Hae Chan HA
;
Seungbeom HONG
;
Minsun CHANG
;
Dae Kyong KIM
Author Information
1. Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea. kimdk@cau.ac.kr
- Publication Type:Original Article
- Keywords:
Paraquat;
RAW264.7 cells;
Apoptosis;
Mitochondria;
ROS
- MeSH:
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
- From:Biomolecules & Therapeutics
2015;23(5):407-413
- CountryRepublic of Korea
- Language:English
-
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.
