PUBLICATION
Microcystin-LR induces angiodysplasia and vascular dysfunction through promoting cell apoptosis by the mitochondrial signaling pathway
- Authors
- Wang, Q., Liu, Y., Guo, J., Lin, S., Wang, Y., Yin, T., Gregersen, H., Hu, T., Wang, G.
- ID
- ZDB-PUB-181130-11
- Date
- 2018
- Source
- Chemosphere 218: 438-448 (Journal)
- Registered Authors
- Wang, Guixue, Wang, Qilong, Wang, Yeqi
- Keywords
- Angiodysplasia, Blood vessel, Cell apoptosis, Microcystin-LR, Zebrafish
- MeSH Terms
-
- Angiodysplasia/chemically induced*
- Animals
- Apoptosis/drug effects*
- Apoptosis Regulatory Proteins/metabolism
- Human Umbilical Vein Endothelial Cells
- Humans
- Microcystins/toxicity*
- Mitochondria/metabolism*
- Signal Transduction/drug effects*
- Vascular Diseases/physiopathology
- Zebrafish/growth & development
- Zebrafish/metabolism
- PubMed
- 30485828 Full text @ Chemosphere
Citation
Wang, Q., Liu, Y., Guo, J., Lin, S., Wang, Y., Yin, T., Gregersen, H., Hu, T., Wang, G. (2018) Microcystin-LR induces angiodysplasia and vascular dysfunction through promoting cell apoptosis by the mitochondrial signaling pathway. Chemosphere. 218:438-448.
Abstract
The harmful algal blooms are becoming increasingly problematic in the regions that drinking water production depends on surface waters. With a global occurrence, microcystins are toxic peptides produced by multiple cyanobacterial genera in the harmful algal blooms. In this study, we examined the effects of microcystin-LR (MC-LR), a representative toxin of the microcystin family, on vascular development in zebrafish and the apoptosis of human umbilical vein endothelial cells (HUVECs). In zebrafish larvae, MC-LR induced angiodysplasia, damaged vascular structures and reduced lumen size at 0.1 μM and 1 μM, leading to the decrease of the blood flow area in the blood vessels and brain hemorrhage, which showed that MC-LR could dose-dependently inhibit vascular development and cause vascular dysfunction. In MC-LR treated HUVECs, the proportion of early apoptosis and late apoptosis cells increased in a concentration-dependent manner. Different concentrations of MC-LR could also activate caspase 3/9 in HUVECs, increase the level of mitochondrial ROS and reduce mitochondrial membrane potential. Additionally, MC-LR could promote the expression of p53 and inhibit the expression of PCNA. The findings showed that MC-LR could promote apoptosis of HUVECs through the mitochondrial signaling pathway. Combined with these results, MC-LR may promote vascular endothelial cell apoptosis through mitochondrial signaling pathway, leading to angiodysplasia and vascular dysfunction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping