Autophagy and proteotoxicity in cardiomyocytes
Autophagy and proteotoxicity in cardiomyocytes
复制标题
心肌细胞的自噬和蛋白毒性
作者：
J. Robbins
越来越多的证据表明，错误折叠的蛋白质和细胞内聚集体会导致心脏病和心力衰竭。我们希望确定ATG7诱导的自噬是否足以减少蛋白质错误折叠应激心肌细胞中错误折叠的蛋白质和聚集体的含量。我们在培养的心肌细胞中使用功能丧失和功能获得的方法来确定ATG7基因敲除和ATG7过表达在由突变的AB晶体蛋白(CryABR120G)的表达诱导的基于蛋白质构象的毒性中的影响，该突变AB晶体蛋白(CryABR120G)已知导致人类心脏病。我们发现ATG7诱导了基础自噬，并挽救了错误折叠的蛋白和聚集在心肌细胞中的CryAB积聚。
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 (CryABR120G) 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.