The Cardiac Metabolism Laboratory, The Feinstein Institute for Medical Research, Long Island Jewish Medical Center, 270-05 76th Avenue, Suite B-387, New Hyde Park, NY 11042, USA.
Cardiovasc Res. 2010 Jan 15;85(2):303-11. doi: 10.1093/cvr/cvp321. Epub 2009 Sep 30.
The ubiquitin-proteasome system (UPS) represents the major pathway for degradation of intracellular proteins. This article reviews the major components and configurations of the UPS including the 26S proteasome and 11S activated proteasome relevant to myocardial ischaemia. We then present the evidence that the UPS is dysfunctional during myocardial ischaemia as well as potential consequences of this, including dysregulation of target substrates, many of them active signalling proteins, and accumulation of oxidized proteins. As part of this discussion, potential mechanisms, including ATP depletion, inhibition by insoluble protein aggregates, and oxidation of proteasome and regulatory particle subunits, are discussed. Finally, the evidence suggesting a role for the UPS in ischaemic preconditioning is presented. Much of this is inferential but clearly indicates the need for additional research.
泛素-蛋白酶体系统 (UPS) 是细胞内蛋白质降解的主要途径。本文综述了 UPS 的主要组成部分和结构，包括与心肌缺血相关的 26S 蛋白酶体和 11S 激活蛋白酶体。然后，我们提出了 UPS 在心肌缺血期间功能失调的证据，以及由此产生的潜在后果，包括靶底物的失调，其中许多是活性信号蛋白，以及氧化蛋白的积累。在这部分讨论中，讨论了潜在的机制，包括 ATP 耗竭、不溶性蛋白聚集体的抑制以及蛋白酶体和调节颗粒亚基的氧化。最后，提出了 UPS 在缺血预处理中作用的证据。其中大部分是推论性的，但清楚地表明需要进一步研究。
