PUBLICATION
Fucoxanthin Prevents 6-OHDA-Induced Neurotoxicity by Targeting Keap1
- Authors
- Wu, W., Han, H., Liu, J., Tang, M., Wu, X., Cao, X., Zhao, T., Lu, Y., Niu, T., Chen, J., Chen, H.
- ID
- ZDB-PUB-210330-8
- Date
- 2021
- Source
- Oxidative medicine and cellular longevity 2021: 6688708 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Carrier Proteins/metabolism*
- Kelch-Like ECH-Associated Protein 1/metabolism*
- Neurotoxicity Syndromes*/metabolism
- Neurotoxicity Syndromes*/pathology
- Neurotoxicity Syndromes*/prevention & control
- Oxidopamine/toxicity*
- PC12 Cells
- Rats
- Xanthophylls/pharmacology*
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- PubMed
- 33777321 Full text @ Oxid Med Cell Longev
Citation
Wu, W., Han, H., Liu, J., Tang, M., Wu, X., Cao, X., Zhao, T., Lu, Y., Niu, T., Chen, J., Chen, H. (2021) Fucoxanthin Prevents 6-OHDA-Induced Neurotoxicity by Targeting Keap1. Oxidative medicine and cellular longevity. 2021:6688708.
Abstract
As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin (FUC) is considered to have excellent neuroprotective activity. However, the target of FUC for its neuroprotective properties remains largely unclear. Oxidative stress is one of the initiating factors causing neuronal cell loss and necrosis, and it is also an important inducement of Parkinson's disease (PD). In the present study, the neuroprotective effect of FUC was assessed using a 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity model. FUC suppressed 6-OHDA-induced accumulation of intracellular ROS, the disruption of mitochondrial membrane potential, and cell apoptosis through the Nrf2-ARE pathway. Keap1 as a repressor of Nrf2 can regulate the activity of Nrf2. Here, the biolayer interferometry (BLI) assay demonstrated that FUC specifically targeted Keap1 and inhibited the interaction between Keap1 and Nrf2. FUC bound to the hydrophobic region of Keap1 pocket and formed hydrogen bonding interactions with Arg415 and Tyr525. Besides, it also dose-dependently upregulated the expressions of antioxidant enzymes, such as nicotinamide heme oxygenase-1, glutamate-cysteine ligase modifier subunit, and glutamate-cysteine ligase catalytic subunit, in 6-OHDA-induced PC12 cells. In 6-OHDA-exposed zebrafish, FUC pretreatment significantly increased the total swimming distance of zebrafish larvae and improved the granular region of the brain tissue damage. These results suggested that FUC could protect the neuronal cells against 6-OHDA-induced injury via targeting Keap1.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping