Age-related changes of alpha-crystallin aggregate in human lens.
Lens alpha-crystallin, composed of two subunits alpha A- and alpha B-crystallin, forms large aggregates in the lens of the eye. The present study investigated the aggregate of human lens alpha-crystallin from elderly and young donors. Recombinant alpha A- and alpha B-crystallins in molar ratios of alpha A to alpha B at 1:1, corresponding to the aged sample, were also studied in detail. We found by ultra-centrifugation analysis that the alpha-crystallin aggregate from elderly donors was large and heterogeneous with an average sedimentation coefficient of 30 S and a range of 20-60 S at 37 degrees C. This was higher compared to the young samples that had an average sedimentation coefficient of 17 S. The sedimentation coefficients of recombinant alpha A- and alpha B-crystallins were approximately 12 S and 15 S, respectively. Even when recombinant alpha-crystallins were mixed in molar ratios equivalent to those found in vivo, similar S values as the native aged alpha-crystallin aggregates were not obtained. Changes in the self-association of alpha-crystallin aggregate were correlated to changes in chaperone activity. Alpha-crystallin from young donors, and recombinant alpha A- and alpha B-crystallin and their mixtures showed chaperone activity, which was markedly lost in samples from the aged alpha-crystallin aggregates.
Fujii
N
N
Research Reactor Institute, Kyoto University, Kumatori, Sennan, Osaka, Japan. nfujii@HL.rri.kyoto-u.ac.jp
Shimmyo
Y
Y
Sakai
M
M
Sadakane
Y
Y
Nakamura
T
T
Morimoto
Y
Y
Kinouchi
T
T
Goto
Y
Y
Lampi
K
K
D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007908:Lens, Crystalline / Q000737:chemistry / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014461:Ultracentrifugation; D038201:alpha-Crystallins / Q000737:chemistry / Q000378:metabolism; D038204:beta-Crystallins / Q000737:chemistry / Q000378:metabolism
D018832:Molecular Chaperones; D011994:Recombinant Proteins; D038201:alpha-Crystallins; D038204:beta-Crystallins