Functional alterations of cardiac proteasomes under physiological and pathological conditions.
The cardiac proteasome is a complex, heterogeneous, and dynamic organelle. Its function is regulated by its molecular organization, post-translational modifications, and associated partner proteins. Pressure overload, ischaemic heart disease, or genetic mutations in contractile proteins can cause heart failure, during which misfolded protein levels are elevated. At the same time, numerous interconnected signal transduction pathways are activated that may modulate any of the three proteasomal regulatory mechanisms mentioned above, resulting in functional changes in cardiac proteasomes. Many lines of evidence support the important role of the ubiquitin-proteasome system (UPS) in the development of heart diseases. Many researchers have focused on the UPS, applying new drug discovery methods not only in the field of cancer research but also in cardiovascular fields such as cardiac hypertrophy and ischaemic heart diseases. More understanding of UPS in the pathophysiology of heart diseases will lead to new routes for therapy.
Tsukamoto
Osamu
O
Department of Cardiovascular Medicine, National Cardiovascular Center, Suita 565-8565, Japan.
Minamino
Tetsuo
T
Kitakaze
Masafumi
M
D000818:Animals; D001794:Blood Pressure; D002312:Cardiomyopathy, Hypertrophic / Q000201:enzymology / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D006331:Heart Diseases / Q000201:enzymology* / Q000209:etiology; D006333:Heart Failure / Q000201:enzymology; D006801:Humans; D017202:Myocardial Ischemia / Q000201:enzymology; D009205:Myocarditis / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000502:physiology*; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits; D025801:Ubiquitin / Q000378:metabolism*; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D025801:Ubiquitin; D000099163:Myosin Binding Protein C