Age-dependent inhibition of proteasome chymotrypsin-like activity in the retina

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The proteasome plays a fundamental role in processes essential for cell viability. A loss in proteasome function has been associated with aging, as well as a number of age-related diseases. Defining the mechanism(s) behind this loss in function will add important information regarding the molecular basis for aging. In the current study, we performed an age-based comparison of proteasome function and composition of subunits and regulatory proteins in the neural retina and retinal pigment epithelium (RPE) in Fischer 344 rats. In the RPE, there was no age-dependent difference in activity, subunit composition, or content of proteasome regulators, PA28 and PA700. In contrast, the aged neural retina demonstrated a significant reduction in the chymotrypsin-like activity and decreased degradation of both casein and casein modified by 4-hydroxynonenal. This loss in function could not be explained by differences in subunit composition, content of PA28 and PA700, or reversible modification of cysteine residues. To begin investigating the molecular basis for the age-associated decrement in proteasome function, we modified the cysteine residues in proteasome from young rats with the sulfhydryl-reactive chemical N-ethylmaleimide. We observed inhibition of the chymotrypsin-like activity and decreased degradation of casein that was comparable to that seen in aged retinas. Thus, chemical modification of cysteine provides an in vitro method that partially recapitulates aging proteasome. Further studies are required to confirm irreversible modification of functionally significant cysteine as a potential mechanism behind the age-related loss in proteasome function.

Original languageEnglish (US)
Pages (from-to)646-654
Number of pages9
JournalExperimental Eye Research
Volume84
Issue number4
DOIs
StatePublished - Apr 1 2007

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Chymotrypsin
Proteasome Endopeptidase Complex
Retina
Cysteine
Caseins
Retinal Pigment Epithelium
Ethylmaleimide
Inbred F344 Rats
Protein Subunits
Cell Survival

Keywords

  • aging
  • chymotrypsin-like activity
  • proteasome
  • retina
  • retinal pigment epithelium

Cite this

Age-dependent inhibition of proteasome chymotrypsin-like activity in the retina. / Kapphahn, Rebecca J.; Bigelow, Erin J.; Ferrington, Deborah A.

In: Experimental Eye Research, Vol. 84, No. 4, 01.04.2007, p. 646-654.

Research output: Contribution to journalArticle

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