Abstract

Introduction

Materials and Method

Results and Discussion

References

Discussion
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Half-lives of proteins introduced into mouse hepatocytes by osmotic procedure were extended in the cells from old animals ( 23-38 month-old) by about 50 to 100% compared with young counterparts (3-10 month-old). Oxidized forms of lysozyme were more rapidly degraded than unoxidized ones in the cells from both young and old mice. The half-life of oxidized lysozymes in the cells from old mice was significantly longer than that in cells from young animals (Ishigami and Goto: Arch. Biochem. Biophys. 277,189 -195, 1990; Goto et al., In: Oxidative Stress and Aging.(eds. Cutler et al., Birkh$B3V(Bser Verlag Basel/Switzerland, pp.151-158;1995Takahashi et al. in preparation). The degradation of oxidized lysozymes was inhibited by a proteasome inhibitor but not by inhibitors of lysosomal enzymes. We previously identified a protease as insulin degrading enzyme in rat liver extracts which degrades oxidatively modified proteins preferentially (Kurochkin and Goto: FEBS Lett. 345, 33-37, 1994). A bona fide physiological role(s) of the enzyme remains unclear, however. The activity of this enzyme did not appear to change with age. Other proteases which have been suggested to be involved in the degradation of oxidatively modified proteins include a proteasome. Activities of peptidases in both 26S and 20S proteasomes of rat livers separated on glycerol gradient declined with advancing age, peptidyl gluamylpeptide hydrolyzing (PGPH) activity being most remarkable, 60 % less in the old compared with the young (Hayashi and Goto: Mech. Ageing Dev. 102, 55-66, 1998). Interestingly, the amount of proteasome proteins did not change with age, suggesting that the enzyme subunit(s) is modified or conformation of the enzyme is altered in the old. It thus appears that accumulation of oxidized or otherwise altered forms of proteins in old animals is partly due to slow degradation of such proteins. We speculate that alteration of proteasomes could constitute a part of vicious cycle which would cause increase in the potentially harmful altered proteins in aged organisms.

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Presentation Number SAgoto0502
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