PUBLICATION
Cadmium-induced dysfunction of the blood-brain barrier depends on ROS-mediated inhibition of PTPase activity in zebrafish
- Authors
- Zhang, T., Xu, Z., Wen, L., Lei, D., Li, S., Wang, J., Huang, J., Wang, N., Durkan, C., Liao, X., Wang, G.
- ID
- ZDB-PUB-210209-4
- Date
- 2021
- Source
- Journal of hazardous materials 412: 125198 (Journal)
- Registered Authors
- Wang, Guixue
- Keywords
- BBB, CdCl(2), Cerebral hemorrhage, Junctional disruption, Reactive oxygen
- MeSH Terms
-
- Animals
- Blood-Brain Barrier*
- Cadmium/toxicity
- Cadmium Chloride/toxicity
- Reactive Oxygen Species
- Zebrafish*
- PubMed
- 33550130 Full text @ J. Hazard. Mater.
Citation
Zhang, T., Xu, Z., Wen, L., Lei, D., Li, S., Wang, J., Huang, J., Wang, N., Durkan, C., Liao, X., Wang, G. (2021) Cadmium-induced dysfunction of the blood-brain barrier depends on ROS-mediated inhibition of PTPase activity in zebrafish. Journal of hazardous materials. 412:125198.
Abstract
Increasing evidence has demonstrated that cadmium accumulation in the blood increases the risk of neurological diseases. However, how cadmium breaks through the blood-brain barrier (BBB) and is transferred from the blood circulation into the central nervous system is still unclear. In this study, we examined the toxic effect of cadmium chloride (CdCl2) on the development and function of BBB in zebrafish. CdCl2 exposure induced cerebral hemorrhage, increased BBB permeability and promoted abnormal vascular formation by promoting VEGF production in zebrafish brain. Furthermore, in vivo and in vitro experiments showed that CdCl2 altered cell-cell junctional morphology by disrupting the proper localization of VE-cadherin and ZO-1. The potential mechanism involved in the inhibition of protein tyrosine phosphatase (PTPase) mediated by cadmium-induced ROS was confirmed with diphenylene iodonium (DPI), a ROS production inhibitor. Together, these data indicate that BBB is a critical target of cadmium toxicity and provide in vivo etiological evidence of cadmium-induced neurovascular disease in a zebrafish BBB model.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping