title: Autophagy and proteotoxicity in cardiomyocytes.
abstract: Increasing evidence suggests that misfolded proteins and intracellular aggregates contribute to cardiac disease and heart failure. We wished to determine if autophagic induction by Atg7 is sufficient to reduce misfolded protein and aggregate content in protein misfolding-stressed cardiomyocytes. We used loss- and gain-of-function approaches in cultured cardiomyocytes to determine the effects of ATG7 knockdown and Atg7 overexpression in protein conformation-based toxicity induced by expression of a mutant aB crystallin (CryAB (R120G) ) known to cause human heart disease. We show that Atg7 induces basal autophagy and rescues the CryAB accumulation of misfolded proteins and aggregates in cardiomyocytes.
authors.affiliation: Division of Molecular Cardiovascular Biology, The Heart Institute, Cincinnati Children's Hospital, Cincinnati, OH, USA.
authors.forename: J Scott
authors.initials: JS
authors.lastname: Pattison
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Robbins
mesh_terms: D000818:Animals; D001343:Autophagy; D002318:Cardiovascular Diseases / Q000378:metabolism; D020868:Gene Silencing; D006333:Heart Failure / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000378:metabolism
chemical_list: C059215:CRYAB protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D038203:alpha-Crystallin B Chain