Protein oxidation and loss of protease activity may lead to cataract formation in the aged lens |
| |
Authors: | Allen Taylor and Kelvin J A Davies |
| |
Institution: | a USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111, USA b Institute for Toxicology and Department of Biochemistry, The University of Southern California, 1985 Zonal Avenue, HSC-PSC 614–616, Los Angeles, CA 90033, USA |
| |
Abstract: | Over 95% of the dry mass of the eye lens consists of specialized proteins called crystallins. Aged lenses are subject to cataract formation, in which damage, cross-linking, and precipitation of crystallins contribute to a loss of lens clarity. Cataract is one of the major causes of blindness, and it is estimated that over 50,000,000 people suffer from this disability. Damage to lens crystallins appears to be largely attributable to the effects of UV radiation and/or various active oxygen species (oxygen radicals, 1O2, H2O2, etc.). Photooxidative damage to lens crystallins is normally retarded by a series of antioxidant enzymes and compounds. Crystallins which experience mild oxidative damage are rapidly degraded by a system of lenticular proteases. However, extensive oxidation and cross-linking severely decrease proteolytic susceptibility of lens crystallins. Thus, in the young lens the combination of antioxidants and proteases serves to prevent crystallin damage and precipitation in cataract formation. The aged lens, however, exhibits diminished antioxidant capacity and decreased proteolytic capabilities. The loss of proteolytic activity may actually be partially attributable to oxidative damage which proteases (like any other protein)_can sustain. We propose that the rate of crystallin damage increases as antioxidant capacity declines with age. The lower protease activity of aged lens cells may be insufficient to cope with such rates of crystallin damage, and denatured crystallins may begin to accumulate. As the concentration of oxidatively denatured crystallins rises, cross-linking reactions may produce insoluble aggregates which are refractive to protease digestion. Such a scheme could explain many events which are known to contribute to cataract formation, as well as several which have appeared to be unrelated. This hypothesis is also open to experimental verification and intervention. |
| |
Keywords: | Proteolysis Protein degradation Protein cross-linking Eye Aging Free radicals Antioxidants Oxidative stress Cataract Ubiquitin ATP |
本文献已被 ScienceDirect 等数据库收录! |
|