Proteinoxidation und Proteolyse w�hrend der zellul�ren Alterung

Abstract

One of the hallmarks of the aging process is the accumulation of oxidized proteins. Therefore, the accumulation of oxidized proteins is one of the key factors in the aging process. Oxidized proteins are normally repaired or degraded by the proteasomal system. This system is the most important intracellular protein degradation machinery, responsible for the degradation of oxidized proteins. For unknown reasons the removal of oxidized proteins is disturbed in aged cells. This leads to the accumulation of non-functional proteins. Further studies are needed for a better understanding of the changes in the proteasomal system and the interference with these changes.

Oxidative Stress in Aging Human Skin

“…The proteasome cannot degrade these aggregates due to steric/mechanic inhibition and remains bound to the structure, unavailable for other substrates [ 229 ]. In addition to that, the proteasome loses efficiency in age resulting in even more accumulation of modified proteins [ 230 , 231 ]. It was demonstrated that the proteasomal activity decreases significantly beginning in middle aged (60 ± 8 years) skin samples, especially in the dermis.…”

“…Autophagic uptake and transport to the lysosome is the most efficient way of removing/containing oxidized proteins after aggregates have formed. This is especially important for old, postmitotic cells which cannot dilute their protein aggregates through cell division [ 207 ] and where the proteasome has lost efficiency and is even more inhibited by the formation of lipofuscin [ 230 , 231 ]. Nevertheless, the progressive oxidation of proteins severely impacts the cell’s metabolism, even in younger cells.…”

Oxidation Proteomics: The Role of Thiol Modifications

“…Because many different proteins are modified, it is evident that many metabolic pathways and signaling cascades are influenced and modulate many physiological and patho-physiological cellular processes. This figure was adapted from various sources (Berk et al, 2008;Bonaventura et al, 2002;Hess et al, 2005;Hipkiss, 2006;(Humphries et al, 2006;Klaunig and Kamendulis, 2004;Lamprecht et al, 2004;Passos and Von Zglinicki, 2006;Petropoulos and Friguet, 2006;Poppek and Grune, 2004;Stadtman and Levine, 2000;Wouters et al, 2007;Ying et al, 2007). Second messengers influence protein expression and kinases and phosphatases in signaling cascades.…”