Proteasome inhibitors and cardiac cell growth.
Activation of the ubiquitin-proteasome system has been described in different models of cardiac hypertrophy. Cardiac cell growth in response to pressure or volume overload, as well as physiological adaptive hypertrophy, is accompanied by an increase in protein ubiquitination, proteasome subunit expression, and proteasome activity. Importantly, an inhibition of proteasome activity prevents and reverses cardiac hypertrophy and remodelling in vivo. The focus of this review is to provide an update about the mechanisms by which proteasome inhibitors affect cardiac cell growth in adaptive and maladaptive models of cardiac hypertrophy. In the first part, we summarize how the proteasome affects both proteolysis and protein synthesis in a context of cardiac cell growth. In the second part, we show how proteasome inhibition can prevent and reverse cardiac hypertrophy and remodelling in response to different conditions of overload.
Hedhli
Nadia
N
Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, MSB G-609, Newark, NJ 07103, USA.
Depre
Christophe
C
D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D061988:Proteasome Inhibitors; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000187:drug effects
D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011506:Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex