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)

1. The effects of free radicals on the capacity of beta L-crystallin to act as a substrate for the enzyme transglutaminase were investigated. 2. beta L-Crystallin was exposed to defined radical species that were generated radiolytically, and transglutaminase activity, using the modified protein as substrate, was subsequently measured by monitoring the incorporation of [14C]putrescine. 3. Exposure of beta L-crystallin to hydroxyl radicals, thymine peroxyl radicals and acetone peroxyl radicals at concentrations of up to 135 microM increased the capacity of the protein to incorporate putrescine. With higher concentrations of these radicals this capacity of beta L-crystallin to act as a transglutaminase substrate declined to control levels or lower. 4. Superoxide radicals were inactive in this regard; hydroperoxyl radicals were active only at high concentrations. 5. It has previously been suggested that changes in the crystallins that occur during aging and with cataract may be due to oxidative reactions and to transglutaminase activity. This study suggests that these phenomena may be considered together rather than separately.
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PMID:Exposure of beta L-crystallin to oxidizing free radicals enhances its susceptibility to transglutaminase activity. 167 15

The most prevalent proteins in the lens of the eye are called crystallins, and it is thought that aberrant crystallins may cause opacification of lens tissue. The Philly mouse, a strain with an inherited cataract, has an abnormal beta B2-crystallin, the principal beta-crystallin in the mouse. The cDNA that codes for the beta B2-crystallin protein has been cloned and sequenced from both the normal and the cataractous Philly mouse. The normal mouse beta B2 cDNA is 756 nucleotides in length with 618 nucleotides of open reading frame. An in-frame deletion of 12 nucleotides has occurred in the Philly mouse cDNA, which results in the loss of 4 amino acids. The sequence of the mutant beta B2 was analyzed against the reported structure of the normal bovine beta B2-crystallin determined by x-ray crystallography. The region, in which the deletion of the amino acids occurs near the COOH terminus, is essential for the formation of the tertiary structure of the beta B2-crystallin. The loss of these residues could explain the alterations that are seen with the Philly beta B2 protein and may account for the instability of the Philly beta B2 protein. This abnormal beta B2-crystallin may be the cause of the cataract in this animal.
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PMID:Deletion mutation in an eye lens beta-crystallin. An animal model for inherited cataracts. 170 74

The amounts of human lens crystallins in the aqueous humor from various types of cataract patients were measured by radioimmunoassay. alpha, beta and gamma-crystallins as antigens for radioimmunoassay were purified from one-year-old normal human lens by TSK3000SW gel permeation column using high performance liquid chromatography. The amounts of both alpha- and gamma-crystallin in the aqueous humor from the patients with cortical and posterior subcapsular cataract were relatively low but in the case of mature cataract those of both crystallins increased. While the amounts of beta-crystallin in aqueous humor from cortical and posterior subcapsular cataract patients were at the same level compared with alpha-crystallin, those from mature cataract patients showed extremely high values.
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PMID:[Lens crystallin leakage in aqueous humor from human cataractous lenses]. 175 46

The IR technique has been applied to investigate secondary structure of the crystallins from the normal bovine eye. Crystallins have been isolated by column chromatography. IR spectra were recorded for the solid phase of proteins. From these spectra, especially amide I, amide II and amide V bands, the presence of alpha-helix, beta-sheet, beta-chain and unordered structures is stated. It was elucidated that alpha-crystallins are present mainly in a beta-sheet conformation but they also contain a considerable quantity of alpha-helix and a slight quantity of unordered and beta-chain forms. In beta H-crystallins, alpha-helix and, in a lesser percentage, beta-structures predominante. beta-sheet, alpha-helix and a low content of beta-chain forms are present in beta L-crystallins. In gamma-crystallins all forms secondary structure have been found, with predominance of beta-sheet and alpha-helix forms. A satisfactory agreement has been noticed between the forms of secondary structures in crystallins investigated by the IR technique and the results obtained by means of other methods. In conclusion IR spectroscopy has been suggested to be applied to observe crystallin structure during formation and development of a cataract.
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PMID:IR spectra of lens crystallins. 191 37

This preliminary report has two parts. The first is based upon data obtained from a group of cataract patients in southern Florida (USA) with the object of relating the types of cataracts removed to their personal background and their protein biochemistry. Intra-capsular cataract surgery patients at the Venice Eye Clinic (Florida) were interviewed, and their extracted lenses were classified. The parameters were: age, place of residency, occupation, medical and family history and indoor/outdoor activity. Subcapsular cataracts were found mainly in the youngest patients and in those who were in Florida the least. Mixed cataracts predominated in the oldest patients, while non-nuclear cataracts were associated most with outdoor activity. Water-insoluble protein was elevated in nuclei of lenses with nuclear opacities. Soluble proteins in the nuclei of nuclear cataracts had increased levels of voided (heavy) protein, beta-crystallins, and less than 20 Kd peptides. The above changes were enhanced in brunescent cataracts. In lenses with cortical opacities, only increased size heterogeneity in the beta-crystallin region was observed. The second part of this report is based upon direct measurements of the optical properties of freshly extracted intra-capsular cataracts obtained in Rochester, New York (USA). The purpose was to attempt to learn the relative contributions that absorption, scattering, and fluorescence make toward obscuring vision. A general conclusion is that the shorter wavelengths of radiant energy in environmental lighting influence the above-stated optical properties the most, and thus appear to be the major contributors to obscured vision.
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PMID:Relationships between human cataracts and environmental radiant energy. Cataract formation, light scattering and fluorescence. 191 41

There is evidence that ibuprofen and paracetamol can act as anti-cataract drugs. [14C]-Ibuprofen labelled at the methyl group of the propanoic acid moiety was synthesized. The labelled ibuprofen was found to bind non-covalently to alpha-crystallin but not to beta- and gamma-crystallin of the bovine lens. Labelled paracetamol binds to total lens soluble proteins. Both drugs penetrate into the lens cortex and nucleus within 24 hr. Affinity chromatographic studies suggest that the lipophilic isobutyl group of ibuprofen hinders binding to the lens proteins. Hence, in the light of weak binding of ibuprofen and paracetamol and strong binding of the ibuprofen analogue used in the affinity chromatography, it is suggested, in this paper, that the protection against cataract by these analgesics is possibly due to their metabolites interacting with the lens proteins.
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PMID:Investigations of ibuprofen and paracetamol binding to lens proteins to explore their protective role against cataract. 195 25

Crystallin glycation seems to play an important role in the development of diabetic cataract. In order to understand the role of glycation in cataractogenesis, levels of glycation of different crystallins were determined by in vitro glycation of rat lens soluble fraction with 50 mM glucose or glucose-6-phosphate (G6P) for up to 5 days and in streptozotocin-diabetic rats during various stages of cataract development. All samples were reduced with [3H]NaBH4 and the tritium incorporation was taken as a measure of glycation. Proteins were routinely separated by molecular sieve HPLC. In vitro studies with glucose showed that gamma-crystallin was readily glycated and reached a plateau by 3 days, while alpha- and beta-crystallins were glycated slowly initially up to 3 days followed by a steep increase as seen on the fifth day. Incubation with 50 mM G6P resulted in an approximately two fold increase in glycation compared to glucose of all crystallins. In the diabetic animals also gamma-crystallin glycation increased approximately twofold within 15 days after the onset of diabetes and an additional threefold within the next 45 days followed by a slight decrease during the following 90-120 days. Increase in glycation, on the contrary, was very slow up to 30 days for alpha-crystallin and up to 60 days for beta-crystallin, followed by a steep increase during the remainder of the experimental period. The high molecular weight (HMW) aggregates had higher levels of glycation than other proteins; the insoluble HMW aggregates contained higher levels of glycation than the soluble HMW aggregates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential glycation of rat alpha-, beta- and gamma-crystallins. 203 22

Congenic hereditary cataract mice, BALB/c-nct/nct, were established by introducing the nct gene from Nakano into BALB/c mice. These mice developed a milder cortical form of cataract which developed sporadically and later in life than in Nakano mice. Combined use of BALB/c and BALB/c-nct/nct mice enables biochemical comparison of normal clear lenses, congenic clear lenses which are destined to be opacified some time later, and opacified lenses in the same genetic and aging statuses. We compared the age-related changes in water content and water-soluble and -insoluble fractions among these three types of lenses. Congenic clear lenses and opaque lenses were more similar to BALB/c normal clear lenses and Nakano opaque ones, respectively, in these parameters. These results suggest, in addition to formation of aggregated crystallins and their accumulation in water-insoluble fractions, that decreased protein synthesis, increased protein degradation and augmented leakage of crystallin might have a significant role in the nct-induced lens opacification.
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PMID:Biochemical evidence for conversion to milder form of hereditary mouse cataract by different genetic background. 206 20

Five months after selenite injection, 58% of the rats that had developed cataract earlier underwent a reversal of the cortical opacity. The purpose of this study was to determine if lenses undergoing recovery from cortical opacity reestablish their ability to retain crystallins. By direct ELISA method, the aqueous humor (AH) of control rats was found to contain 18, 39 and 10 ng/ml alpha-, beta- and gamma-crystallin, respectively, while vitreous humor (VH) contained 43, 98 and 23 ng/ml of alpha-, beta- and gamma-crystallin, respectively. In rats with mature cataracts which did not recover by 5 months after selenite injection, there was an approximately 10-fold greater crystallin concentration in the AH and about 20 times greater crystallin concentration in the VH than in the controls. In contrast, rats undergoing recovery from cortical cataract showed almost normal concentration of crystallins in the AH. While crystallins were still elevated in the VH of the rats undergoing recovery from cortical cataract, the crystallin content was lower than in the rats which did not recover. Higher crystallin concentrations in the VH could be explained by either a greater loss through the posterior capsule, or a slower turnover of VH. Decreased crystallin loss from lenses undergoing recovery suggested that the recovered lens at least partly reestablishes its ability to retain crystallins. These data may demonstrate that the lens fiber permeability is lowered while lens repair is occurring.
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PMID:Changes in crystallin concentration in rat aqueous and vitreous humors after selenium-induced reversible cortical cataract. 208 66

The mechanism of lens protein aggregation with age and/or cataract formation was investigated using the peptides resolubilized from the insoluble protein fraction of normal and cataractous human lenses. The insoluble fraction was treated with reductants for cleaving disulfide bonds, or with chelating agents for removing calcium ions from the aggregates. This study demonstrates that the insoluble protein aggregates consist of an approximately 400 Kd complex, which is formed by the peptides with lower molecular weight. Protein aggregation in the cataractous lens might be caused by disulfide bonds whereas, in aging, the aggregate might be preferentially formed by calcium ion bridges rather than by disulfide bonds. It was observed that the aggregate from the cataractous lenses involved a peptide with a molecular mass lower by 1 Kd or 2 Kd than the peptides found in the normal lens. The composition of crystallins in aggregating proteins and their secondary structures were also different in the normal and the cataractous lenses. Such changes of molecular weight, conformation, and/or crystallin species in the lens may lead to the disintegration of the orderly arrangement of crystallins, resulting in the diffused reflection and lens opacities which are seen in senile cataract.
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PMID:Characterization of water-insoluble proteins in normal and cataractous human lens. 221 64


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