Ubiquitin and ubiquitin conjugates in human lens.
Ubiquitin, an 8.5 kDa polypeptide found almost universally in plants and animals, is a normal component in the lens. The best documented function for ubiquitin involves its conjugation to proteins as a signal to initiate degradation. Conjugates for ubiquitin-dependent degradation tend to be of very high molecular mass and are rapidly degraded. Another role of ubiquitin conjugation may be as a stabilizer during stress for protection of constituent proteins, resulting in ubiquitin conjugates that are long-lived. Examination of clear and cataractous human lenses of < 1 to > 50 years revealed the dramatic accumulation of ubiquitin and ubiquitin conjugates with age, beginning at approximately 10 years. Epithelial tissue contained predominantly conjugates of > 250 kDa, although ubiquitin conjugates were found at 98 and 40-60 kDa in tissues from older donors. The water-soluble, urea-soluble and urea-insoluble fractions of lens cortex and core also contain ubiquitin conjugates that accrue with age. High molecular mass conjugates (> 250 kDa) are particularly prominent in older lens tissue. Cataractous lenses, as compared with normal lenses of the same age, show more of these high molecular mass conjugates in the urea-soluble and urea-insoluble fractions of cortex and core. Heterogeneous conjugates in the 20-85 kDa range accumulate in an age-related fashion in all lens cortex and core fractions. While levels of free ubiquitin are significant in the epithelium and the water-soluble cortex and core for all ages, there is no detectable free ubiquitin in the urea-soluble and urea-insoluble fraction under conditions used in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
Jahngen-Hodge
J
J
Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.
Cyr
D
D
Laxman
E
E
Taylor
A
A
D000375:Aging / Q000502:physiology*; D001345:Autoradiography; D004848:Epithelium; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007908:Lens, Crystalline / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
D005136:Eye Proteins; D014452:Ubiquitins