Cadmium-induced dysfunction of the blood-brain barrier depends on ROS-mediated inhibition of PTPase activity in zebrafish

Zhang, Tao; Xu, Zichen; Wen, Lin; Lei, Daoxi; Li, Shuyu; Wang, Jinxuan; Huang, Jinxia; Wang, Nan; Durkan, Colm; Liao, Xiaoling; Wang, Guixue

doi:10.1016/j.jhazmat.2021.125198

Cited by 50 publications

(25 citation statements)

References 51 publications

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“…For instance, Cd 2+ are likely to bind to various proteins and regulatory elements, thereby disrupting redox homeostasis and communication of signals [ 25 ]. The Cd 2+ -induced increase of oxidative stress can be considered an etiological factor in a variety of nervous system diseases [ 26 , 27 , 28 ]. In brief, Cd has been commonly recognized to pose great threats to the central nervous system (CNS).…”

Section: Introductionmentioning

confidence: 99%

Wnt/β-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging

Liu

Tian

et al. 2022

IJMS

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Cadmium (Cd) is a toxic heavy metal and worldwide environmental pollutant which seriously threatens human health and ecosystems. It is easy to be adsorbed and deposited in organisms, exerting adverse effects on various organs including the brain. In a very recent study, making full use of a zebrafish model in both high-throughput behavioral tracking and live neuroimaging, we explored the potential developmental neurotoxicity of Cd2+ at environmentally relevant levels and identified multiple connections between Cd2+ exposure and neurodevelopmental disorders as well as microglia-mediated neuroinflammation, whereas the underlying neurotoxic mechanisms remained unclear. The canonical Wnt/β-catenin signaling pathway plays crucial roles in many biological processes including neurodevelopment, cell survival, and cell cycle regulation, as well as microglial activation, thereby potentially presenting one of the key targets of Cd2+ neurotoxicity. Therefore, in this follow-up study, we investigated the implication of the Wnt/β-catenin signaling pathway in Cd2+-induced developmental disorders and neuroinflammation and revealed that environmental Cd2+ exposure significantly affected the expression of key factors in the zebrafish Wnt/β-catenin signaling pathway. In addition, pharmacological intervention of this pathway via TWS119, which can increase the protein level of β-catenin and act as a classical activator of the Wnt signaling pathway, could significantly repress the Cd2+-induced cell cycle arrest and apoptosis, thereby attenuating the inhibitory effects of Cd2+ on the early development, behavior, and activity, as well as neurodevelopment of zebrafish larvae to a certain degree. Furthermore, activation and proliferation of microglia, as well as the altered expression profiles of genes associated with neuroimmune homeostasis triggered by Cd2+ exposure could also be significantly alleviated by the activation of the Wnt/β-catenin signaling pathway. Thus, this study provided novel insights into the cellular and molecular mechanisms of Cd2+ toxicity on the vertebrate central nervous system (CNS), which might be helpful in developing pharmacotherapies to mitigate the neurological disorders resulting from exposure to Cd2+ and many other environmental heavy metals.

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Section: Introductionmentioning

confidence: 99%

Wnt/β-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging

Liu

Tian

et al. 2022

IJMS

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“…The presence of EHS was also detected in brain and gonadal tissues, indicating that EHS could cross the blood-brain barrier and blood-testis barrier and increase the risk of neurotoxicity and transgenerational toxicity. 48,49 Similar to gill tissue, skin tissue can also be in direct contact with the exposure solution, while the mucus layer secreted on the skin surface becomes the main resistance to the enrichment of target pollutants, resulting in a lower level of occurrence. 50 Muscle is the tissue with the lowest cumulative concentration of EHS, possibly because EHS is lipophilic and muscle tissue has a low fat content, which leads to a low affinity between EHS and muscle tissue.…”

Section: Resultsmentioning

confidence: 99%

Effects of polystyrene nanoplastics on the bioaccumulation, distribution and parental transfer of ethylhexyl salicylate

Zhou

Yan

et al. 2022

Environ. Sci.: Nano

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“…In the hemorrhagic shock group, the tight junctions of VECs were damaged, the density of tight junctions was reduced, wide gaps appeared, and shedding was observed ( Figure 1F ). The adherent junction protein (VE-cadherin) and tight junction protein (ZO-1) are key proteins involved in regulating vascular permeability ( Yokota et al, 2021 ; Zhang et al, 2021 ). The results showed that following hemorrhagic shock, the expression of junction proteins, such as ZO-1 and VE-cadherin, was significantly decreased ( Figure 1E ).…”

Section: Resultsmentioning

confidence: 99%

The protective effect of pericytes on vascular permeability after hemorrhagic shock and their relationship with Cx43

Zhang

Peng

et al. 2022

Front. Physiol.

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Vascular hyperpermeability is a complication of hemorrhagic shock. Pericytes (PCs) are a group of mural cells surrounded by microvessels that are located on the basolateral side of the endothelium. Previous studies have shown that damage to PCs contributes to the occurrence of many diseases such as diabetic retinopathy and myocardial infarction. Whether PCs can protect the vascular barrier function following hemorrhagic shock and the underlying mechanisms are unknown. A hemorrhagic shock rat model, Cx43 vascular endothelial cell (VEC)-specific knockdown mice, and VECs were used to investigate the role of PCs in vascular barrier function and their relationship with Cx43. The results showed that following hemorrhagic shock, the number of PCs in the microvessels was significantly decreased and was negatively associated with an increase in pulmonary and mesenteric vascular permeability. Exogenous infusion of PCs (106 cells per rat) colonized the microvessels and improved pulmonary and mesenteric vascular barrier function. Upregulation of Cx43 in PCs significantly increased the number of PCs colonizing the pulmonary vessels. In contrast, downregulation of Cx43 expression in PCs or knockout of Cx43 in VECs (Cx43 KO mice) significantly reduced PC colonization in pulmonary vessels in vivo and reduced direct contact formation between PCs and VECs in vitro. It has been suggested that PCs have an important protective effect on vascular barrier function in pulmonary and peripheral vessels following hemorrhagic shock. Cx43 plays an important role in the colonization of exogenous PCs in the microvessels. This finding provides a potential new shock treatment measure.

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Cadmium-induced dysfunction of the blood-brain barrier depends on ROS-mediated inhibition of PTPase activity in zebrafish

Cited by 50 publications

References 51 publications

Wnt/β-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging

Wnt/β-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging

Effects of polystyrene nanoplastics on the bioaccumulation, distribution and parental transfer of ethylhexyl salicylate

The protective effect of pericytes on vascular permeability after hemorrhagic shock and their relationship with Cx43

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