Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After early life, the dry weight of normal human lenses increases at a relatively constant rate with time. Transformation from soluble to insoluble material appears to occur at a comparable rate, resulting in a constant amount of soluble material. However, in cataract the insolubilization rate is accelerated. These observations are supported by determination of D-aspartic acid/L-aspartic acid ratios. The abundance of D-aspartic acid increases with aging at a constant rate in the insoluble fraction of normal lenses but does not change in the soluble fraction. However, in cataractous lenses there is a significant decrease in the ratio in the insoluble fraction. Examination of polypeptides isolated from reduced and alkylated soluble and insoluble cataractous lens proteins as well as other data suggest the following additional conclusions: (i) the 10,000-dalton polypeptide in the insoluble fraction is derived in part from degradation of an already insoluble precursor; and (ii) the lowered abundance of D-aspartic acid in the insoluble fraction of cataractous lenses is primarily due to the rapid insolubilization of the 43,000- and 20,000-dalton range components.
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PMID:Racemization in human lens: evidence of rapid insolubilization of specific polypeptides in cataract formation. 27 77

A 43,000-dalton polypeptide has been isolated from the high-molecular-weight disulfide-rich fraction of the water-insoluble protein of human cataractous lenses. On the basis of immunochemical reactivity and fluorescent antibody binding, this polypeptide is localized in the membrane region of the lens cell. This observation suggests an interaction between the soluble lens proteins and membrane-associated polypeptides in the formation of large protein aggregates which may cause cataract.
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PMID:An extrinsic membrane polypeptide associated with high-molecular-weight protein aggregates in human cataract. 37 84

Senile nuclear cataractous lenses were divided into three groups of increasing nuclear color. These groups were considered as successive stages in the development of senile nuclear cataract. The cortex and the nucleus of normal and cataractous lenses were separated into water-soluble, urea-soluble and urea-insoluble fractions. Fractionation on a Sephadex G-200 column of the water-soluble components revealed five protein fractions for both cortex and nucleus. Only minor quantitative differences in polypeptide chain composition were found by isoelectric focusing between corresponding protein fractions isolated from normal and cataractous lenses. The weight percentages of the water-soluble, urea-soluble, and urea-insoluble fractions of cortex and nucleus from the normal and cataractous lenses were determined. A decrease of the amounts of the water-soluble and urea-soluble fractions and a concomitant increase of the urea-insoluble fraction were observed in the nucleus as a function of cataract development. Lens wet weight and protein content did not change significantly. The carbohydrate content of the urea-soluble fractions increased, that of the urea-insoluble fraction decreased. A striking decrease of the phospholipid content in the urea-insoluble fraction was found.
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PMID:Protein changes in the human lens during development of senile nuclear cataract. 93 70

Short-term incubation of bovine alpha-crystallin with ascorbate alters the protein conformational stability. The denaturation curves with urea and guanidinium-chloride show different patterns, suggesting a deviation from a two-state mechanism owing to the presence of one or more intermediates in the unfolding of ascorbate-modified alpha-crystallin. Furthermore, the latter protein profiles are shifted to lower denaturant concentrations indicating a destabilizing action of ascorbate, which is capable of facilitating protein dissociation into subunits as demonstrated by gel filtration with 1.5 M-urea. The decrease in conformational stability cannot be ascribed to any major structural alteration, but rather to localized changes in the protein molecule. In fact, no difference between native and ascorbate-treated alpha-crystallin can be detected by amino acid analysis but perturbation of the tryptophan and tyrosine environment is indicated by alterations in intrinsic fluorescence. Furthermore, turbidity and light-scattering measurements suggest an involvement of the lysine side chains, since aggregability patterns with acetylsalicylic acid are significantly altered. The ascorbate-destabilizing effect on the conformational stability of alpha-crystallin, probably exerted through oxidative modification of amino acid residues and/or the formation of covalent adducts, provokes unfavourable steric interactions between residues along the polypeptide chains, thus favouring aggregation and insolubilization of crystallins which can lead to cataract formation, as also demonstrated by proteolytic digestion patterns which show a lower rate of degradation of the ascorbate-modified alpha-crystallin.
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PMID:Conformational stability of bovine alpha-crystallin. Evidence for a destabilizing effect of ascorbate. 141 62

L-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of GSH biosynthesis, was administered four times daily to mouse pups on post-natal days 7 and 8, inducing initiation of opacification on day 9. The initial progression of the cataract (less than 24 hr) was divided into four stages: (1) developing floriform; (2) mature floriform; (3) degenerate floriform; and (4) amorphous translucent cataract. Following this, dense corticonuclear opacities developed within several days. Two-dimensional gel electrophoresis of water-soluble whole lens extracts indicated that the most rapid early cataractous changes, occurring mainly during stage 2, were loss of the two major components of the heavy beta-crystallin fraction, a 31-kDa basic polypeptide and an acidic component at 27 kDa, concomitant with the appearance of new species at 30 and 25 kDa. This was followed by more extensive modification of both alpha and beta-crystallins during stages 3 and 4 and the appearance of abnormal species at 26, 19 and 18 kDa, which were slightly more acidic than the major normal alpha A-crystallin polypeptide. The gamma-crystallin components, relatively unaffected at stage 4, were then lost rapidly as dense opacities ensued. By contrast with the water-soluble fraction, the normal day 9 urea-soluble fraction was deficient in gamma-crystallin polypeptides and enriched in anodic components whose relative electrophoretic mobilities were similar to those reported previously for phosphorylated bovine alpha A-crystallin and several cytoskeletal polypeptides. At stage 4 of the cataract, the modifications of normal alpha and beta-crystallin components in the urea-soluble fraction paralleled those in the water-soluble fraction, but the products seen were more numerous. In addition, the cytoskeletal proteins were no longer detectable. Substantial increases in lens Ca2+ that precede all of the above changes in lens polypeptide composition suggest that Ca(2+)-activated proteolysis may play a major role in development of BSO cataracts.
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PMID:Progressive modifications of mouse lens crystallins in cataracts induced by buthionine sulfoximine. 162 46

Cataracts previously have been shown to occur spontaneously in aged Hannover Wistar rats. The morphology and time course of opacification of these cataracts are very similar to those appearing in the human lens, where it has been previously shown that the major intrinsic polypeptide (MIP26K) of the fiber cell membrane undergoes covalent modification during cataractogenesis. To ascertain possible biochemical similarities between the two cataract systems, antisera were made against synthetic peptides corresponding to the sequence of MIP26K to probe Western blots of lens proteins from transparent versus opaque lenses from normal aged rats. The results of this analysis showed that these antisera can detect the presence of covalent changes occurring in the MIP26K molecule during the development of cortical opacities in the normal aged rat.
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PMID:Changes in lens membrane major intrinsic polypeptide during cataractogenesis in aged Hannover Wistar rats. 200 29

Exposure of cultured rabbit lens epithelial cells to repetitive doses of UV-B radiation delays their growth and alters the synthesis of specific proteins. Irradiated cells on the shoulder of the survival curve exhibited a dose-dependent decrease in growth when subcultured in serum-supplemented medium. UV-B irradiation did not affect the subsequent attachment efficiency of the cells. Control and UV-B irradiated cells were incubated with [35S]methionine and the pattern of protein synthesis in the cells was analyzed by SDS-PAGE and autoradiography. Analysis of the labeled proteins from cells exposed to UV-B radiation showed the induction of a 32 kD polypeptide and the loss of a 26 kD polypeptide compared with controls. Analysis of the proteins released by the UV-B irradiated cells into the culture medium revealed the 50% loss of a 37 kD radiolabeled protein compared with controls. The alteration of protein synthesis in lens epithelial cells by UV-B radiation may contribute to cataract formation.
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PMID:Effect of ultraviolet-B radiation on protein synthesis in cultured lens epithelial cells. 209 21

The composition and origin of the urea soluble polypeptides which accumulate in the U18666A rat-cataract were studied. Chromatography on Sephacryl S-200 in 7.2 M urea separated the USP into 19-20 and 22-26 kDa enriched fractions. The polypeptide composition of these fractions was probed by immunoblotting of IEF and 2-D electrophoresis gels. The cataract USP largely focused at pHs comparable to alpha- and beta-crystallins. Immunoblotting of 2-D gels showed the USP to be composed predominantly of alpha- and beta-derived crystallins; little gamma-polypeptide was detected in the gels. Some of the insoluble alpha-crystallin appeared to be degraded. Changes in the lens WSP which accompanied the increase in USP were also measured. WSP decreased more than USP increased. Decreases in soluble high molecular weight proteins (alpha- plus beta-crystallins) and medium molecular weight proteins (beta-crystallins) were calculated which together could entirely account for the increased USP. An unexpected decrease in the lens soluble low molecular weight proteins (gamma-crystallins) appeared largely due to the selective leakage of gammas from the lens. The protein content of the ocular humors from eyes with cataracts increased 4 fold and contained polypeptides that focused on IEF like gamma-light crystallin and reacted with the gamma-crystallin antiserum. The cause of the protein insolubilization in the U18666A cataract is unknown but could be partially due to increased aggregation of alpha-crystallins secondary to loss of gamma-crystallins from the lens.
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PMID:On the composition and origin of the urea-soluble polypeptides of the U18666A cataract. 224 43

The study has examined the effects of the SH-oxidizing agent diamide (Diazane dicarboxylic acid bis-(N,N-dimethyl-amide)) on the water-soluble portion of proteins from rabbit lenses. The dialyzed protein extracts were incubated for 1-1.5 hrs with various concentrations of diamide. Treatments were monitored for alterations in sulphydryl contents, gel filtration and gel electrophoresis profiles of proteins. The response to 2 mM diamide treatment for 1 hr consists of rapid oxidation (up to 40%) of protein-bound sulphydryl groups accompanied by an appearance of polypeptides with apparent molecular weights. The protein with molecular weight of 29 kilodaltons was shown to be involved in cross-linking. The linkages in the dialyzed water-soluble lens polypeptide fraction induced by diamide may be reduced by GSH (10 mM) treatment of protein extract. The main target of oxidative insult induced by diamide in the water-soluble proteins of the lens is probably the superficially localized sulphydryl groups of crystallins. Our observations suggest that the described oxidative system of proteins may be a useful tool for cataract research.
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PMID:[Oligomerization of water soluble proteins of rabbit crystalline lens under the action of diamide]. 226 11

Congenital nuclear cataracts transmitted by an autosomal dominant gene are present in a line of strain 13/N guinea-pigs. Studies on the lens proteins from these animals demonstrate changes in both the composition and structure of the crystallins relative to normal controls. The most prominent difference is in the zeta-crystallin, a taxon-specific crystallin which has been shown to be related to the alcohol dehydrogenases. In animals homozygous for the cataract phenotype the normal zeta-crystallin polypeptide is absent from the lens. Quantitation is difficult in the cataractous lenses from heterozygotes because of protein changes secondary to opacification: however in liver and kidney which have catalytic levels of the protein, the concentrations are approximately half that present in tissue from normal control animals. These findings suggest that in the cataractous animals a mutation has occurred in the gene for zeta-crystallin. In addition, a novel protein which is very similar to zeta-crystallin is synthesized only in the lenses of animals with cataract. This protein appears to be the product of the mutant gene for zeta-crystallin. These data support the hypothesis that this hereditary congenital cataract results from a specific mutation in the zeta-crystallin gene.
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PMID:Association of hereditary cataracts in strain 13/N guinea-pigs with mutation of the gene for zeta-crystallin. 231 75


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