Age-dependent declines in proteasome activity in the heart.
The proteasome is a major intracellular proteolytic system involved in the removal of oxidized and ubiquitinated protein and the induction of certain stress response pathways. In this study, age-dependent alterations in proteasome function were investigated to gain insight into potential factors which contribute to increased susceptibility to various forms of heart disease during aging. Proteasome activity in cellular extracts prepared from Fisher 344 rat hearts was found to decrease with age. These declines in activity were associated with a decreased 20S proteasome content and loss of specific activities. As determined by two-dimensional gel electrophoresis of purified 20S proteasome, the distribution and silver staining intensities of enzyme subunits were found to vary with age, suggesting that alterations in proteasome subunit composition and/or structure are involved in age-related declines in proteasome activity. In addition, age-dependent increases in the levels of oxidized and ubiquitinated proteins, known substrates of the proteasome, were observed. Thus, loss in proteasome function may impair the ability of myocytes to mount an appropriate response to stress, thereby enhancing the susceptibility of the aging heart to cardiovascular disease.
Bulteau
Anne-Laure
AL
Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement, Université Denis Diderot-Paris 7, 2 Place Jussieu, Paris Cedex 05, 75251, France.
Szweda
Luke I
LI
Friguet
Bertrand
B
D000375:Aging / Q000378:metabolism*; D000818:Animals; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D010084:Oxidation-Reduction; D046988:Proteasome Endopeptidase Complex; D021122:Protein Subunits; D051381:Rats; D011916:Rats, Inbred F344; D025801:Ubiquitin / Q000378:metabolism
D009097:Multienzyme Complexes; D021122:Protein Subunits; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex