自噬
医学
基因敲除
细胞生物学
蛋白酶体
肌节
基因剔除小鼠
病态的
热休克蛋白
热休克蛋白70
下调和上调
蛋白质稳态
内科学
心肌细胞
生物
细胞凋亡
生物化学
受体
基因
作者
Svante Gersch,Manar Elkenani,Gerd Hasenfuß,Susanna Lutz,Karl Toischer,Belal A. Mohamed
出处
期刊:Circulation
[Ovid Technologies (Wolters Kluwer)]
日期:2017-11-14
摘要
Background: The heat shock protein HSPA4 is a member of HSP70 family known to play a role in cell survival under stress conditions. We previously reported that HSPA4 protein is induced in pathologically-remodeled hearts of mice and humans. Furthermore, classical Hspa4 knockout mice exhibit exaggerated pathological remodeling, concomitant with aggregation of polyubiquitinated proteins, but maintained proteasome activity. Objective: We sought to investigate the potential cardioprotective role of HSPA4 and to provide insights into the underlying mechanisms. Methods and Results: Hearts from Hspa4 knockout mice displayed increased expression of LC3-II, Beclin-1 and p62 proteins, suggesting a robust accumulation of autophagosomes and impaired autophagy flux. Consistently, RNAi-mediated HSPA4 knockdown augmented pathological remodeling in neonatal rat cardiomyocytes (NRCMs) treated with enthothelin-1 or phenylephrine, as demonstrated by increased cardiomyocyte size, pronounced sarcomere rearrangement, and enhanc...
科研通智能强力驱动
Strongly Powered by AbleSci AI