The interplay between autophagy and the ubiquitin-proteasome system in cardiac proteotoxicity.
The interplay between autophagy and the ubiquitin-proteasome system in cardiac proteotoxicity.
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DOI：
10.1016/j.bbadis.2014.07.028
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发表时间：
2015-02
影响因子：
6.2
通讯作者：
Wang, Xuejun
中科院分区：
文献类型：
--
作者：
Wang, Changhua;Wang, Xuejun
蛋白质毒性是指受损/错误折叠的蛋白质对细胞的有害影响。心肌特别容易受到蛋白质毒性的影响，因为持续和严重的蛋白质毒性应激会导致细胞死亡，而心肌的自我更新能力非常有限。泛素-蛋白酶体系统（UPS）和自噬-溶酶体途径（ALP）是大多数细胞蛋白降解的两个主要途径。UPS和ALP功能的改变与心脏中蛋白质毒性物质的积累有关，这是常见心脏病的一个关键病理特征，包括特发性、缺血性、压力过载心肌病和很大一部分充血性心力衰竭。新出现的证据表明，蛋白酶体抑制或损伤会激活自噬，相反，急性ALP抑制有时会增加内在的蛋白酶体肽酶活性，但慢性ALP抑制会阻碍UPS在泛素化蛋白降解中的表现。这两种降解途径相互作用的确切分子基础在很大程度上仍不清楚。在这里，我们回顾了目前对UPS和自噬在心脏蛋白质毒性控制中的作用的理解，并特别关注这两种途径之间的串扰。
Proteotoxicity refers to the detrimental effects of damaged/misfolded proteins on the cell. Cardiac muscle is particularly susceptible to proteotoxicity because sustained and severe proteotoxic stress leads to cell death and cardiac muscle has very limited self-renewal capacity. The ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway (ALP) are two major pathways responsible for degradation of most cellular proteins. Alterations of UPS and ALP functions are associated with the accumulation of proteotoxic species in the heart, a key pathological feature of common forms of heart disease including idiopathic, ischemic, and pressure-overloaded cardiomyopathies and a large subset of congestive heart failure. Emerging evidence suggests proteasome inhibition or impairment activates autophagy and conversely, acute ALP inhibition may sometimes increase intrinsic proteasome peptidase activities but chronic ALP inhibition hinders UPS performance in ubiquitinated protein degradation. The exact molecular basis on which the two degradative pathways interact remains largely undefined. Here we review current understanding of the roles of the UPS and autophagy in the control of cardiac proteotoxicity, with a specific focus on the crosstalk between the two pathways.
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影响因子：
29
作者：
Dong S;Jia C;Zhang S;Fan G;Li Y;Shan P;Sun L;Xiao W;Li L;Zheng Y;Liu J;Wei H;Hu C;Zhang W;Chin YE;Zhai Q;Li Q;Liu J;Jia F;Mo Q;Edwards DP;Huang S;Chan L;O'Malley BW;Li X;Wang C
通讯作者：
Wang C
影响因子：
6.6
作者：
Bruening, Ansgar;Rahmeh, Martina;Friese, Klaus
通讯作者：
Friese, Klaus
影响因子：
2.9
作者：
Ishii, T;Sakurai, T;Uchida, K
通讯作者：
Uchida, K
DOI：
10.1084/jem.187.1.97
发表时间：
1998-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Griffin TA;Nandi D;Cruz M;Fehling HJ;Kaer LV;Monaco JJ;Colbert RA
通讯作者：
Colbert RA
影响因子：
3.3
作者：
Kaushik, Susmita;Massey, Ashish C.;Cuervo, Ana Maria
通讯作者：
Cuervo, Ana Maria