Oxidative stress, aging and the proteasomal system.
Oxygen free radicals and other oxidants are causing potential danger for intracellular proteins during the lifetime of cells and organisms. Therefore, protein oxidation is one of the natural consequences of aerobic life. The degradation of non-functional, oxidized proteins is an essential part of the antioxidant defenses of cells. The major proteolytic system responsible for the removal of oxidized cytosolic proteins is the proteasomal system. This system consists of the 20S 'core' proteasome and a multitude of various regulators. It is known that certain components of this system are regulated during oxidative stress and aging. One of the highlights of age-related changes of cellular metabolism is the accumulation of oxidized proteins. The question whether the accumulation of oxidized proteins during aging is due to a malfunction of the intracellular proteolytic machinery of the cell remains still unsolved. The information available about an age-related decline of the proteasomal system is very contradictory. The current literature about the proteasomal system, the regulation of this system during oxidative stress and the age-related changes are in the focus of this review.
Grune
T
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Clinics of Physical Medicine and Rehabilitation, Medical Faculty (Charité), Humboldt University Berlin, Schumannstr. 20/21, D-10098 Berlin, Germany. tilman.grune@charite.de
D000375:Aging / Q000378:metabolism*; D000818:Animals; D003432:Cross-Linking Reagents; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism
D003432:Cross-Linking Reagents; D009097:Multienzyme Complexes; D011506:Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex