PUBLICATION
Tcap deficiency impedes striated muscle function and heart regeneration with elevated ROS and autophagy
- Authors
- Zhao, Y., Liang, J., Liu, X., Li, H., Chang, C., Gao, P., Du, F., Zhang, R.
- ID
- ZDB-PUB-240904-4
- Date
- 2024
- Source
- Biochimica et biophysica acta. Molecular basis of disease 1870(8): 167485 (Journal)
- Registered Authors
- Zhang, Ruilin
- Keywords
- Mitophagy, Muscular dystrophy, Tcap, Ventricle regeneration, Zebrafish
- MeSH Terms
-
- Muscle, Striated/metabolism
- Muscle, Striated/pathology
- Reactive Oxygen Species*/metabolism
- Animals
- Regeneration*
- Connectin/genetics
- Connectin/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Heart/physiology
- Heart/physiopathology
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- Cardiomyopathies/genetics
- Cardiomyopathies/metabolism
- Cardiomyopathies/pathology
- Autophagy*
- Zebrafish*
- PubMed
- 39226992 Full text @ BBA Molecular Basis of Disease
Citation
Zhao, Y., Liang, J., Liu, X., Li, H., Chang, C., Gao, P., Du, F., Zhang, R. (2024) Tcap deficiency impedes striated muscle function and heart regeneration with elevated ROS and autophagy. Biochimica et biophysica acta. Molecular basis of disease. 1870(8):167485.
Abstract
Telethonin/titin-cap (TCAP) encodes a Z-disc protein that plays important roles in sarcomere/T-tubule interactions, stretch-sensing and signaling. Mutations in TCAP are associated with muscular dystrophy and cardiomyopathy; however, the complete etiology and its roles in myocardial infarction and regeneration are not fully understood. Here, we generated tcap gene knockout zebrafish with CRISPR/Cas9 technology and observed muscular dystrophy-like phenotypes and abnormal mitochondria in skeletal muscles. The stretch-sensing ability was inhibited in tcap-/- mutants. Moreover, Tcap deficiency led to alterations in cardiac morphology and function as well as increases in reactive oxygen species (ROS) and mitophagy. In addition, the cardiac regeneration and cardiomyocyte proliferation ability of tcap-/- mutants were impaired, but these impairments could be rescued by supplementation with ROS scavengers or autophagy inhibitors. Overall, our study demonstrates the essential roles of Tcap in striated muscle function and heart regeneration. Additionally, elevations in ROS and autophagy may account for the phenotypes resulting from Tcap deficiency and could serve as novel therapeutic targets for muscular dystrophy and cardiomyopathy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping