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)

Antisera have been made to synthetic peptides corresponding to the expected tryptic fragments from the C-terminal region of human alpha A2 crystallin (T19 corresponds to residues 158-163; T20 corresponds to residues 164-173). These antisera were used on conjunction with a sensitive radioimmunoassay, to identify the elution times of peptides resolved on a C18 column from a tryptic digest of water soluble and water insoluble proteins from the human lens. Isolation and purification of the peptides reactive with the anti-peptide sera, followed by the use of tandem mass spectrometry to determine the amino acid sequences in the peptides, demonstrated that the antisera reacted specifically with the T19 and T20 sequences. Using the antisera specific for the T19 sequence, analysis of the peptides resolved from tryptic digests of individual lenses demonstrated no major differences between the elution profiles of five normal vs. ten cataractous lenses, while analysis of the same digests with the antiserum to the T20 sequence demonstrated major changes in reactivity and/or elution time of tryptic peptides from eight of the cataractous lenses analyzed. Together, these studies strongly suggest that during human cataract formation, covalent changes occur in the C-terminal region of the alpha A2 molecule. In addition, these studies provide the general methodology, whereby antisera specific for known sequences of a polypeptide chain, can be used to locate the sequences involved in covalent modification during the process of senile cataractogenesis of the human lens.
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PMID:Analysis of tryptic peptides from the C-terminal region of alpha-crystallin from cataractous and normal human lenses. 237 63

Soluble lens crystallins from 6-10-week-old, galactose-fed, male Sprague-Dawley rats were analyzed by two-dimensional polyacrylamide gel electrophoresis at each of the five Sippel stages of cataractogenesis. Electrophoretograms were compared with similarly analyzed crystallins from comparably aged, chow-fed controls. Polypeptides were assigned to crystallin families and subfamilies on the basis of chromatographic fractionations with Sephadex G-200, superfine. Staining intensities of polypeptides from control lenses remained essentially unchanged throughout the experimental period, while those of the polypeptides from cataractous lenses showed non-uniform changes. Staining of the genomic gamma-crystallins increases up to at least stage 3; by stage 4, staining of gamma-chains, with perhaps those of gamma 5 and gamma 6 excepted, diminishes and in the total cataract, staining of all chains is further reduced. With possibly the addition of one chain, the total number of postsynthetically modified gamma-crystallins in cataractous lenses does not exceed that in the comparably aged normal lens. The genomic alpha- and beta-crystallin polypeptides are sustained close to normal levels up to stages 3 or 2, respectively, after which their gradually falling levels are accompanied by the generation of new species or elevated levels of existing post-translational species. An exception to this behavior is the rapid and total loss of beta B1a, a genomic subunit implicated in the aggregation of beta H-crystallins. Charge heterogeneity and variable pI displayed by beta B1a and other highly cationic beta- and gamma-crystallin polypeptides can be induced during isoelectric focusing and may be due to thiol group oxidation.
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PMID:Differential effects of galactose-induced cataractogenesis on the soluble crystallins of rat lens. 237 84

We have analyzed the consequences of a mutation causing a recessive hereditary cataract in the rat. The lenses of these rats were examined both by histological and molecular biological methods. In the mutant rat lens development starts normally during early fetal life, but becomes progressively disrupted. The structure of the lens is clearly abnormal around the time of birth. Surprisingly, changes at the molecular level occur much later than the histological effects can be observed. Lens epithelial and cortex fiber cells apparently continue to synthesize the lens-specific crystallin mRNAs and proteins in spite of the damaged fiber cells.
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PMID:RNA and protein analysis of an X-ray-induced hereditary cataract in rat. 246 Aug 14

Cataracts were observed in female F344 rats who intravenously received methylnitrosourea (MNU), a potent carcinogen for multiple organs, in one dose of 50 mg/kg body weight. Induction of cataract 40 weeks after MNU treatment was 41% whereas no cataract was observed in control rats. The aggregation of beta H-crystallin fraction by MNU was studied in vitro. HPLC pattern of beta H-crystallin changed when lens protein was incubated for 24 hrs with MNU. HPLC patterns indicated that MNU induced high molecular weight aggregates of beta H-crystallin. This study conveys some indication about the direct interaction of MNU with lens protein in cataract formation.
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PMID:Induction of cataract in methylnitrosourea treated Fischer (F344) rats. 258 61

One possible route to cataract formation may be via the carbamoylation of lens proteins due to increased concentrations of cyanate in the body resulting from uraemia associated with renal failure and with severe diarrhoea. Carbamoylation of gamma-II-crystallin, which is found in the lens core, could alter the surface charge network of the molecules, resulting in aggregation, increased light-scattering and hence cataract. We have attempted to locate the site(s) of carbamoylation in gamma-II-crystallin. gamma-II-Crystallin was isolated by gel chromatography and ion-exchange chromatography. gamma-II-Crystallin was then carbamoylated by incubation with potassium [14C]cyanate, followed by citraconylation and digestion with trypsin to give peptides that were separated by high-resolution ion-exchange chromatography. The amino acid compositions of the radioactive peptides were compared with the expected peptide composition for gamma-II-crystallin. The radioactive peptide compositions, which agreed with the theoretical peptides, all matched with the N-terminal region of gamma-II-crystallin and had in common the presence of the N-terminal glycine residue. It appears that the alpha-amino group of the N-terminal glycine was the main site of carbamoylation. This site forms part of the charge network on the surface of gamma-II-crystallin.
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PMID:Site of carbamoylation of bovine gamma-II-crystallin by potassium [14C]cyanate. 259 Jan 75

The structure, distribution, and nature of scattering elements associated with cold cataract formation in the young rat lens were studied in situ using light and electron microscopy and ImmunoGold electron microscopy. A large accumulation of spherical droplets, ranging from approximately 1.5 microns to 10 microns in diameter, were found in the lens nucleus in cold cataracts induced at 22 degrees C or 4 degrees C in TC-199 culture medium. Many droplets of all sizes were associated with the cell membranes. A cooled and then rewarmed lens was found to lose its opacity and subsequently no droplets were observed, indicating that there was a good correlation between the onset of opacification and the formation of droplets. Electron microscopy showed that droplets were composed of homogeneous electron-dense aggregates without limiting membranes. ImmunoGold study revealed that alpha-, beta-, and gamma-crystallins were all present within each droplet. This study demonstrates that extensive accumulation of the crystallin droplets in the lens nucleus is the contributing factor for the light scattering and opacification of the cold cataract in the young intact rat lens.
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PMID:Visualization of crystallin droplets associated with cold cataract formation in young intact rat lens. 260 83

Normal and streptozotocin diabetic female Wistar rats were given vitamin E in the diet as the tocopherol, acetate, or succinate form (2,850 IU/kg food). At the end of 6 weeks, the rats were examined for weight gain or loss, general body condition, and cataracts. At sacrifice, blood was collected for measurement of serum glucose, and gamma-crystallin levels were measured in aqueous and vitreous humors using a radioimmunoassay. One lens was homogenized in 8 M guanidinium chloride for ATP analysis. In normal rats, gamma-crystallin was detected in both aqueous and vitreous humors, with the higher concentration in the vitreous humor. Diabetes caused a sixfold increase in gamma-crystallin in both the aqueous and vitreous humors. Diabetes also led to a significant worsening in general body condition, loss of body weight, formation of cataracts, and decrease in lens ATP levels. Addition of vitamin E and vitamin E succinate, but not vitamin E acetate, to the diet resulted in reduction of gamma-crystallin leakage into the vitreous humors and an increase in body weight. There was no improvement noted for the lens ATP levels, the general body condition, or visual cataract score. Neither streptozotocin-induced diabetes nor vitamin E in the diet appeared to affect the weight of the lenses.
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PMID:Modeling cortical cataractogenesis: IX. Activity of vitamin E and esters in preventing cataracts and gamma-crystallin leakage from lenses in diabetic rats. 262 5

Eye lens senile cataract is a major cause of blindness, affecting the elderly in particular. The etiology of the disorder has been elusive, and attempts to delay the onset of senile cataracts have been unsuccessful. The need for more information is underscored by epidemiologists who estimate that the ability to delay cataract formation in humans by only 10 years would eliminate the need for 50% of the cataract extractions performed annually in the United States. The Emory mouse provides the best model for human senile cataracts. Feeding Emory mice a diet that was restricted in calories by approximately 21% delayed the onset of cataracts. This is the first study that demonstrates in vivo the delay of senile-type cataracts. In these animals, aging and cataracts are associated with diverse changes in the proportion of various proteins (particularly 21, 22, 31-34 kDa) and with transformation of proteins from a soluble to an insoluble state. In advanced cataracts, there is a loss of total protein. Within a cataract grade, there is no difference between restricted and nonrestricted animals in relative proportion of specific lens proteins or in amounts of total or soluble proteins. The transition from a clear to cataractous lens appears when the soluble-to-total protein ratio falls below about 0.58. The exclusive use of gamma-crystallin as an indicator of lens viability is questioned. To the extent that cataract formation is due to lens protein oxidation and/or an inability to proteolytically remove damaged protein, it would appear that caloric restriction results in enhanced protection against lens oxidative stress or in prolonged proteolytic function.
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PMID:Moderate caloric restriction delays cataract formation in the Emory mouse. 270 7

gamma-Crystallins are a family of low molecular weight proteins found in high concentration in the densely packed regions of high refractive index in vertebrate lenses. Certain members have the characteristic property of a high critical temperature (tc) for phase separation. We report the three-dimensional structure determination of such a protein, bovine lens gamma IVa-crystallin, which has been refined to give an X-ray R-factor of 0.143. Its high tc contrasts with the low tc gamma II-crystallin, whose structure we have already published. The root mean square difference between the alpha-carbon atoms of these two proteins is 0.70 A and gamma IVa has an internal symmetry even higher than that of gamma II. The presence of a protein that exhibits the phenomenon of phase separation at body temperature renders the lens very susceptible to a transformation from transparent to an opaque state due to irregularities in the refractive index. Protein interactions of gamma IVa-crystallin have implications for the mechanism of cataract formation. Modes of self-association behaviour of gamma IVa-crystallin have been inferred from an analysis of the lattice interactions in the crystalline state, where the protein packing density is similar to that of the intact lens. It appears that the point mutation at position 103 from a serine residue in gamma II to a valine in gamma IVa gives rise to a lattice contact formed by two four-stranded beta-sheets in gamma IVa. A group-specific mutation at position 118 from leucine to phenylalanine induces subtle differences in core packing, leading to a reorganization around residue 103. However, the final phase separation determinant may be a complex combination of many side-chain functions.
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PMID:Packing interactions in the eye-lens. Structural analysis, internal symmetry and lattice interactions of bovine gamma IVa-crystallin. 273 25

Cataract is a long-term complication of diabetes mellitus. Diabetics have increased glucosamine levels and it is possible that the non-enzymic glycosylation of the lens structural proteins by glucosamine induces conformational changes in the lens that contribute to cataract formation. Aspirin and aspirin-like analgesics may protect against glycosylation. In this paper the binding of glucosamine to bovine lens proteins and the effects of aspirin, paracetamol and ibuprofen on this reaction were investigated. Significant binding of glucosamine to the lens proteins was found. Gel-chromatography indicated that beta H-crystallin was most reactive to the amino-sugar. Of the analgesics studied, aspirin was the most effective inhibitor of glycosylation, followed by the other anti-inflammatory drug, ibuprofen. Preincubation of the lens homogenate with aspirin was no more effective at decreasing binding of glucosamine than was simultaneous incubation with aspirin. Glutathione significantly inhibited glucosamine binding. Glucosamine is active in non-enzymic glycosylation but the reaction can be inhibited by agents thought to protect against cataract.
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PMID:The non-enzymic glycosylation of bovine lens proteins by glucosamine and its inhibition by aspirin, ibuprofen and glutathione. 275 89


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