PUBLICATION
Accelerated Sarcopenia Phenotype in the DJ-1/Park7-Knockout Zebrafish
- Authors
- Rostad, K.O., Trognitz, T., Frøyset, A.K., Bifulco, E., Fladmark, K.E.
- ID
- ZDB-PUB-250109-181
- Date
- 2024
- Source
- Antioxidants (Basel, Switzerland) 13(12): (Journal)
- Registered Authors
- Fladmark, Kari E., Froyset, AnnKristin
- Keywords
- DJ-1, Parkinson?s disease, mitochondria, park7, sarcopenia, skeletal muscle
- MeSH Terms
- none
- PubMed
- 39765837 Full text @ Antioxidants (Basel)
Citation
Rostad, K.O., Trognitz, T., Frøyset, A.K., Bifulco, E., Fladmark, K.E. (2024) Accelerated Sarcopenia Phenotype in the DJ-1/Park7-Knockout Zebrafish. Antioxidants (Basel, Switzerland). 13(12):.
Abstract
Age-dependent loss of muscle mass and function is associated with oxidative stress. DJ-1/Park7 acts as an antioxidant through multiple signalling pathways. DJ-1-knockout zebrafish show a decline in swimming performance and loss of weight gain between 6 and 9 months of age. Here, we address the degree to which this is associated with muscle degeneration and identify molecular changes preceding dysregulation of muscle performance. Loss of DJ-1 reduced the skeletal muscle fibre cross-section area. The highly mitochondrial-dependent red slow muscle was more affected than the white muscle, and degeneration of sub-sarcolemma red muscle mitochondria was observed. Using TandemMassTag-based quantitative proteomics, we identified a total of 3721 proteins in the multiplex sample of 4 and 12-month-old muscles. A total of 68 proteins, mainly associated with inflammation and mitochondrial function, were dysregulated in the young DJ-1-null adults, with Annexin A3, Sphingomyelin phosphodiesterase acid-like 3B, Complement C3a, and 2,4-dienoyl CoA reductase 1 being the most affected. The loss of DJ-1 also accelerated molecular features associated with sarcopenia, such as a decrease in the NAD+/NADH ratio and a reduction in Prostaglandin reductase 2 and Cytosolic glycerol-3-phosphate dehydrogenase levels. In view of the experimental power of zebrafish, the DJ-1-null zebrafish makes a valuable model for understanding the connection between oxidative stress and age-dependent muscle loss and function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping