PUBLICATION
A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae
- Authors
- Li, R., Zhang, L., Shi, Q., Guo, Y., Zhang, W., Zhou, B.
- ID
- ZDB-PUB-180402-2
- Date
- 2018
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 199: 46-54 (Journal)
- Registered Authors
- Guo, YongYong, Qipeng, Shi, Zhang, Wei, Zhou, BingSheng
- Keywords
- Autophagy, Developmental neurotoxicity, LC3 II, TDCIPP, Zebrafish larvae
- MeSH Terms
-
- Flame Retardants/toxicity
- Microtubule-Associated Proteins/metabolism
- Organophosphorus Compounds/toxicity*
- Butyrylcholinesterase/metabolism
- Neurons/drug effects
- Autophagy/drug effects*
- Embryo, Nonmammalian/drug effects
- Water Pollutants, Chemical/toxicity*
- Zebrafish/growth & development*
- Zebrafish Proteins/metabolism
- Locomotion/drug effects
- Animals
- Larva/drug effects
- Larva/enzymology
- Larva/growth & development
- Acetylcholinesterase/metabolism
- PubMed
- 29605586 Full text @ Aquat. Toxicol.
- CTD
- 29605586
Citation
Li, R., Zhang, L., Shi, Q., Guo, Y., Zhang, W., Zhou, B. (2018) A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae. Aquatic toxicology (Amsterdam, Netherlands). 199:46-54.
Abstract
Tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP), an extensively used organophosphorus flame retardant, is frequently detected in various environmental media and biota, and has been demonstrated as neurotoxic. Autophagy has been proposed as a protective mechanism against toxicant-induced neurotoxicity. The purpose of the present study was to investigate the effect of TDCIPP exposure on autophagy, and its role in TDCIPP-induced developmental neurotoxicity. Zebrafish embryos (2-120?h post-fertilization [hpf]) were exposed to TDCIPP (0, 5, 50 and 500??g/l) and a model neurotoxic chemical, chlorpyrifos (CPF, 100??g/l). The developmental endpoints, locomotive behavior, cholinesterase activities, gene and protein expression related to neurodevelopment and autophagy were measured in the larvae. Our results demonstrate that exposure to TDCIPP (500??g/l) and CPF causes developmental toxicity, including reduced hatching and survival rates and increased malformation rate (e.g., spinal curvature), as well as altered locomotor behavior. The expression of selected neurodevelopmental gene and protein markers (e.g., mbp, syn2a, and ?1-tubulin) was significantly down-regulated in CPF and TDCIPP exposed zebrafish larvae. Treatment with CPF significantly inhibits AChE and BChE, while TDCIPP (0-500??g/l) exerts no effects on these enzymes. Furthermore, the conversion of microtubule-associated protein I (LC3 I) to LC3 II was significantly increased in TDCIPP exposed zebrafish larvae. In addition, exposure to TDCIPP also activates transcription of several critical genes in autophagy (e.g. Becn1, atg3, atg5, map1lc3b and sqstm1). To further investigate the role of autophagy in TDCIPP induced developmental neurotoxicity, an autophagy inducer (rapamycin, Rapa, 1?nM) and inhibitor (chloroquine, CQ, 1??M) were used. The results demonstrate that the hatching rate, survival rate, and the expression of mbp and ?1-tubulin proteins were all significantly increased in larvae treated with TDCIPP (500??g/l) and Rapa compared to TDCIPP alone. In contrast, co-treatment with the autophagy inhibitor CQ results in exacerbated neurodevelopmental toxicity. Taken together, our results confirm that exposure to TDCIPP induces autophagy, which plays a protective role in TDCIPP-induced developmental neurotoxicity in zebrafish embryos and larvae.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping