KAI-CHIEN YANGChuang K.-W.Yen W.-S.Lin S.-Y.Chen H.-H.Chang S.-W.Lin Y.-S.Wu W.-L.Tsao Y.-P.WEN-PIN CHENSHOW-LI CHEN2021-04-152021-04-152019222828https://scholars.lib.ntu.edu.tw/handle/123456789/556539Background: Cardiomyopathy is a common and lethal complication in patients with limb-girdle muscular dystrophy (LGMD), one of the most prevalent forms of muscular dystrophy. The pathogenesis underlying LGMD-related cardiomyopathy remains unclear. NRIP (gene name DCAF6), a Ca2+-dependent calmodulin binding protein, was reduced in dystrophic muscles from LGMD patients. Mice lacking NRIP exhibit a myopathic phenotype resembling that in LGMD patients, making NRIP deficiency a potential culprit leading to cardiomyopathy. This study aimed to determine if NRIP deficiency leads to cardiomyopathy and to explore the underlying molecular mechanisms. Methods and results: NRIP expression was reduced in both human and mouse failing hearts. Muscle-specific NRIP knockout (MCK-Cre[SDGs]SDG3adenosine triphosphate; alpha actinin 2; carrier proteins and binding proteins; F actin; nicotinamide adenine dinucleotide; nicotinic acid; nuclear receptor interaction protein; protein CapZ; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide; transcriptome; unclassified drug; actin; actinin; adenosine triphosphate; calcium; nicotinamide adenine dinucleotide; nicotinic acid; protein binding; reactive oxygen metabolite; receptor interacting protein 140; adult; animal cell; animal experiment; animal model; animal tissue; Article; cardiac muscle cell; cardiomyopathy; clinical article; confocal microscopy; controlled study; gene expression; heart muscle contractility; human; human tissue; immunoprecipitation; in vivo study; male; mitochondrial respiration; mouse; nonhuman; priority journal; protein deficiency; protein expression; protein protein interaction; sarcomere; transcriptomics; transmission electron microscopy; animal; biological model; cardiac muscle; cardiomyopathy; cell respiration; chemistry; down regulation; drug effect; genetics; heart contraction; heart failure; heart mitochondrion; homeostasis; metabolism; pathology; pathophysiology; phenotype; protein domain; sarcomere; ultrastructure; Actinin; Actins; Adenosine Triphosphate; Animals; Calcium; Cardiomyopathies; Cell Respiration; Down-Regulation; Heart Failure; Homeostasis; Humans; Male; Mice; Mitochondria, Heart; Models, Biological; Myocardial Contraction; Myocardium; Myocytes, Cardiac; NAD; Niacin; Nuclear Receptor Interacting Protein 1; Phenotype; Protein Binding; Protein Domains; Reactive Oxygen Species; Sarcomeresjournal article10.1016/j.yjmcc.2019.09.009316297372-s2.0-85073532215