Targeting proteasomes for cardioprotection.
The ubiquitin-proteasome system (UPS) plays a central role in intracellular protein degradation and regulates many cellular processes, including cell proliferation, inflammation, adaptation to stress, cell death, and the removal of damaged or misfolded proteins. Numerous studies have demonstrated that altered UPS function is involved in the pathogenesis of a wide range of cardiac diseases including hypertrophy and failure, myocardial ischemia, atherosclerosis, and diabetic cardiovascular disease. Impairment of proteasome function is a common feature of cardiac disease; however several studies have also demonstrated increased proteasome activity in models similar but not identical with those having decreased function. Recent studies have shown that use of proteasome inhibitors before or following production of the model of cardiac disease may confer cardioprotection under certain conditions.
Yu
Xichun
X
Endocrinology/Harold Hamm Oklahoma Diabetes Center & Heart Rhythm Institute, University of Oklahoma Health Sciences Center, 1200 Everett Dr, Oklahoma City, OK 73104, United States. xichun-yu@ouhsc.edu
Patterson
Eugene
E
Kem
David C
DC
D000818:Animals; D016503:Drug Delivery Systems; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000502:physiology; D006331:Heart Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000502:physiology / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D025801:Ubiquitin / Q000502:physiology
D061988:Proteasome Inhibitors; D025801:Ubiquitin; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease