Deficiency in nebulin repeats of sarcomeric nebulette is detrimental for cardiomyocyte tolerance to exercise and biomechanical stress.

ABSTRACT: The actin-binding sarcomeric nebulette (NEBL) protein provides efficient contractile flexibility via interaction with desmin intermediate filaments. NEBL gene mutations affecting the nebulin repeat (NR) domain are known to induce cardiomyopathy. The study aimed to explore the roles of NEBL in exercise and biomechanical stress response. We ablated exon3 encoding the first NR of Nebl and created global Nebl^ex3-/ex3- knockout mice. Cardiac function, structure, and transcriptome were assessed before and after a 4-wk treadmill regimen. A Nebl-based exercise signaling network was constructed using systems genetics methods. H9C2 and neonatal rat cardiomyocytes (NRCs) expressing wild-type or mutant NEBL underwent cyclic mechanical strain. Nebl^ex3-/ex3- mi

SUBMITTER: Vejandla RM 

PROVIDER: S-EPMC8163647 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature