| dc.description.abstract | A cataract, resulting in blurred vision or even blindness, is a common disease for aged people. It is caused by the light scattering in the eye lens. Nowadays, the regular treatment is to replace the cloudy eye lens with artificial ones. Although the surgery is well developed, it is also
accompanied by high risks. Therefore, developing non-surgical as well as preventive therapies and drugs is an urgent issue in an aging society.
Alpha-crystallin(α-crystallin) is the major water-soluble protein in the eye lens and consists of two subunits, αA and αB, their function is to maintain the native state of other proteins, such as β and γ-crystallin, in the eye lens. That is to retain the transparency of the eye lens by
inhibiting protein aggregation. The function loss of α-crystallin is known as a reason for cataracts.
The results of animal experiments indicate that lanosterol can inhibit the formation of cataracts as well as restore the cloudy lens back to the transparent state. Its mechanism is still a puzzle until now. Sterol molecules generally exist in cell membranes and have a strong interaction with lipids. Furthermore, previous studies show α-crystallins bound to membranes increase with age. We propose a model based on sterol-protein interaction mediated by membranes to clarify the mechanism of inhibition of cataracts induced by sterols.
In this study, αA-crystallin and αB-crystallin were produced via gene transfer, expression, and protein purification. A sterol from plants, ergosterol, DOPC and Di20:1PC lipids were used as model membranes for studying the interactions between α-crystallin, ergosterol, and lipid
membranes. First, the effect of membranes on the chaperone activity of αA and αB was checked by the ADH and lysozyme assays. Then, circular dichroism spectroscopy was used to probe the ratio of α-crystallin binding to membranes. Finally, X-ray diffraction was used to determine the
electron density of the lipid bilayers of the lamellar thin film sample. The structural change of the lipid bilayer induced by α-crystallin and ergosterol binding was extracted from X-ray data. This paper will discuss the observed interaction between ergosterol, α-crystallin and membrans
from the experimental results.
Combining the three experimental results, it was shown that ergosterol not only made the thickness of the membrane thinner, but also made it easier for α-crystallin to bind to membranes and enter membranes. Then, ergosterol could not restore the anti-aggregation ability of αcrystallin caused by membranes. These results are different from the effect of cholesterol on membranes. | en_US |