Identification of apoptosis and macrophage migration events in paraquat-induced oxidative stress using a zebrafish model.
OBJECTIVE
Paraquat (PQ) is a pesticide highly toxic to human beings, and a well-known trigger of oxidative stress. Although several animal models of PQ poisoning have been developed, some disadvantages limit their application in vivo. A zebrafish model was used in the present study to better define mechanisms of oxidative stress injury induced by PQ.


METHODS
The toxicity of PQ was evaluated in the AB strain of zebrafish, and apoptosis was assessed by acridine orange staining. Macrophage migration was identified using the TG (zlyz:EGFP) transgenic strain, and angiogenesis was observed using the fli1a-EGFP casper strain. Following the validation of gene changes by zebrafish-based in vivo quantitative real-time PCR, network analysis was performed using the Ingenuity Pathway Analysis software.


RESULTS
We first established the LC50 of PQ in the zebrafish model, and then found that robust oxidative stress and antioxidant genes were activated after PQ exposure. Moreover, apoptosis and distinct macrophage activation and migration were identified for the first time in PQ-exposed zebrafish. Utilizing this model, both extrinsic and intrinsic pathways involved in PQ-induced apoptosis were elucidated. We further demonstrated that macrophage migration was specifically induced by PQ, and that Rho family members and JNK-MMP13 signaling participated in this process.


CONCLUSIONS
Zebrafish is a promising tool for investigating the mechanisms of oxidative stress injury induced by PQ, and for screening effective anti-oxidant drugs.
Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China.
Qiang
Q
Wang
Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China.
Shuai
S
Liu
Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China.
Dayong
D
Hu
Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China.
Zhen
Z
Wang
Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China.
Ling
L
Wang
Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China; Department of Biomedical Engineering, University of Houston, TX, USA.
Tianfu
T
Wu
Shanghai Research Center for Model Organisms, Shanghai, PR China.
Zhuanbin
Z
Wu
Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China; Department of Biomedical Engineering, University of Houston, TX, USA.
Chandra
C
Mohan
Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China. Electronic address: pengai@tongji.edu.cn.
Ai
A
Peng
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D006540:Herbicides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects*; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000633:toxicity*; D015027:Zebrafish
D006540:Herbicides; D010269:Paraquat
Apoptosis; Macrophage migration; Oxidative stress; Paraquat; Zebrafish model