Endocrinology/Harold Hamm Oklahoma Diabetes Center and Heart Rhythm Institute, University of Oklahoma Health Sciences Center and VAMC, 1200 Everett Dr, Oklahoma City, OK 73104, USA.
Cardiovasc Res. 2010 Jan 15;85(2):312-20. doi: 10.1093/cvr/cvp309. Epub 2009 Sep 10.
The ubiquitin-proteasome system (UPS) plays a central role in protein degradation and regulates a variety of critical cellular processes. During recent years, the cardiac UPS has become increasingly recognized as a key regulator of cardiac function under both physiological and pathological conditions. Numerous studies have demonstrated that altered UPS function is involved in the pathogenesis of cardiac disease including myocardial ischaemia or infarction. The expression and activity of the E3 ubiquitin ligases, which confer substrate specificity in the UPS pathway, affect the apoptosis and severity of disease in myocardial ischaemia and reperfusion. Although impaired proteasome function is commonly associated with myocardial ischaemic injury, recent evidence also supports a cardioprotective role for proteasome inhibitors in myocardial ischaemia. We will review these studies and data, discuss controversies regarding the UPS alterations and use of proteasome inhibitors in myocardial ischaemia, and attempt to identify strategies that may enhance their clinical application.
泛素-蛋白酶体系统（UPS）在蛋白质降解中发挥核心作用，并调节多种关键的细胞过程。近年来，心脏 UPS 已逐渐被认为是生理和病理条件下心脏功能的关键调节者。大量研究表明，UPS 功能的改变参与了包括心肌缺血或梗死在内的心脏疾病的发病机制。E3 泛素连接酶的表达和活性赋予 UPS 途径中的底物特异性，影响心肌缺血再灌注中的细胞凋亡和疾病严重程度。尽管蛋白酶体功能受损通常与心肌缺血损伤有关，但最近的证据也支持蛋白酶体抑制剂在心肌缺血中的心脏保护作用。我们将回顾这些研究和数据，讨论 UPS 改变和蛋白酶体抑制剂在心肌缺血中的应用的争议，并试图确定可能增强其临床应用的策略。
