Avermectin induces toxic effects in insect nontarget cells involves DNA damage and its associated programmed cell death

被引:10
作者
Li, Meng [1 ]
Zhang, Ping [1 ]
Xu, Wenping [1 ]
Yuan, Jianzhong [2 ]
Li, Qingfeng [2 ]
Tao, Liming [1 ]
Li, Zhong [1 ]
Zhang, Yang [1 ]
机构
[1] East China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Sch Pharm, Shanghai 200237, Peoples R China
[2] Chinese Acad Sci, Inst Plant Physiol & Ecol, CAS Ctr Excellence Mol Plant Sci, Shanghai 200032, Peoples R China
来源
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY | 2021年 / 249卷
关键词
Avermectin; Cytotoxicity; DNA damage; Programmed cell death; Sf9; cells; AUTOPHAGY; EXPRESSION; CONFERS; CHAIN; LC3;
D O I
10.1016/j.cbpc.2021.109130
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Avermectin (AVM), is widely applied in the fields of agriculture, possess activities against mites and insects. AVM is generally thought to keep the GABA-related chloride channels open in insect cells. However, AVM induces cytotoxicity in non-neural cells still ambiguous. Here we evaluate the cytotoxicity and other mode of action of AVM in Spodoptera frugiperda (Sf9) cells. Our results showed that AVM suppressed the activity of Sf9 cells and induced programmed cell death. DNA damage of Sf9 cells was detected by alkaline comet assay and PARP. The cleavage of poly ADP-ribose polymerase (PARP) and DNA double-strand breaks demonstrated AVM induced DNA damage in Sf9 cells. In addition, a series of established cytotoxicity tests were conducted to explore the mechanism of AVM toxicity in Sf9 cells. Typical apoptosis changes were occurred including increasing the expression of Bax/Bcl-2 and the activation of caspase-9/-3. Subsequently, Western blotting was used to detected autophagy related proteins including LC3, Beclin1 and p62. We found that AVM upregulated LC3, Beclin1 expression and downregulated p62 expressions. Moreover, we found that AVM induced autophagy may through AMPK/mTORmediated autophagy pathway. These results showed that AVM-induced DNA damage and programmed cell death in Sf9 cells.
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页数:8
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