Proteasome function and protein oxidation in the aged retina.
The proteasomal pathway is responsible for processes essential for cell viability, including the selective degradation of oxidized proteins. An age-dependent loss in proteasome function has been reported in many tissues, but has not been examined in the retina. In this study, we evaluated proteasome function and protein oxidation in retinal homogenates from young adult and old F344BN rats. For retinal proteasome from old rats, we observed an 80% decrease in the rate of casein degradation and a 75% loss in chymotrypsin-like activity. This loss in activity could be partially accounted for by a 50% reduction in expression of the 20S proteasome. The regulatory complex PA700 and the inducible beta-subunit, LMP7, which is associated with the chymotrypsin-like activity, were expressed in equivalent concentrations relative to the 20S catalytic core in both young and old rats. Immunochemical analysis using antibodies that recognize the protein oxidative modifications, nitrotyrosine and 4-hydroxy-2-nonenal, showed that retinal proteins from old rats exhibited the greatest immunoreactivity. These results suggest that the age-related loss in proteasome function contributes to the accumulation of oxidized retinal proteins. Thus, the combined effect of an increase in oxidized proteins and inactivation of the protease responsible for ridding the cell of oxidized proteins places the aged retina at greater risk for irreversible damage caused by oxidative stress.
Louie
Jennifer L
JL
Department of Ophthalmology, University of Minnesota, Minneapolis, MN 55455, USA.
Kapphahn
Rebecca J
RJ
Ferrington
Deborah A
DA
D000375:Aging / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002364:Caseins / Q000378:metabolism; D002918:Chymotrypsin / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000502:physiology*; D005136:Eye Proteins / Q000378:metabolism*; D008297:Male; D009097:Multienzyme Complexes / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D012160:Retina / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000447:Aldehydes; D002364:Caseins; D005136:Eye Proteins; D009097:Multienzyme Complexes; C002744:3-nitrotyrosine; D014443:Tyrosine; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C027576:4-hydroxy-2-nonenal