|Shang, Fu - HNRCA-TUFTS|
|Gong, Xin - HNRCA-TUFTS|
|Palmer, Helen - HNRCA-TUFTS|
|Nowell, Thomas - HNRCA-TUFTS|
|Taylor, Allen - HNRCA-TUFTS|
Submitted to: Experimental Eye Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 21, 1997
Publication Date: N/A
Interpretive Summary: Accumulation of damaged proteins is associated with formation of cataract, a common age-related eye disease. Under normal conditions, damaged proteins are selectively removed from the lens. The ubiquitin pathway is a system which removes damaged proteins. In this study we investigated age-related changes in the activity of this pathway in rat lenses. We also studied the effect of oxidation on the activity of this pathway. We found that the activity of the pathway decreased with aging. Gentle oxidation with hydrogen peroxide resulted in increased activity of the pathway, but the extent of the increase in the old lenses was much less than the increase in young lenses. These data indicate that the activity of the ubiquitin pathway in the lens declines with aging, and the ability to increase the activity of this pathway in response to oxidation is also attenuated upon aging. The age-related decrease in this pathway may contribute to the accumulation of damaged proteins in old lenses.
Technical Abstract: Accumulation of damaged proteins is a major age-related change in lenses and is associated with lens opacification. In many tissues, selective removal of abnormal or damaged proteins occurs via a ubiquitin-dependent proteolytic pathway. In this work, we studied age-related changes in rat lens in the following aspects: levels of the ubiquitin-protein conjugates (UPC); some of the enzymes involved in ubiquitin conjugation in rat lenses; and ability to respond to oxidative damage. The levels of endogenous high molecular weight (HMW) UPC in each developmental zone of the lenses from young rats were higher than those in lenses from old animals. Peroxide treatment generally resulted in elevated levels of endogenous HMW UPC although masses of bulk proteins remained unchanged. The increases in UPC in the epithelial sections of young and old lenses upon oxidative stress were comparable. In the cortex of young lenses, there was a significant oxidation-related increase in UPC. There was a similar trend but diminished response in the cortex of old lenses. Nuclear fibers from young lenses also showed an oxidation-induced increase in the level of UPC. This response was not observed in nuclear fibers of old lenses. The ability to form HMW-ubiquitin conjugates with exogenous 125I-labeled ubiquitin in the lens also increased upon oxidative stress. The extent of the increase in the de novo ubiquitin conjugating activity upon exposure to oxidation in old lens was much smaller than in young lens. These data indicate that the lens has the ability to increase ubiquitin conjugation activity in response to oxidative stress and that this ability is attenuated upon aging.