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)

Large accumulations of postsynthetically oxidized proteins are observed in the aged and cataractous eye lens. Ascorbate has previously been used to delay photooxidative damage in vitro. The goals of this study were to confirm that dietary ascorbate can be used to enhance lens ascorbate levels and to determine if lenses with enhanced ascorbate can better withstand photooxidative stress in the form of ultraviolet (UV) light exposure. Guinea pigs were placed on high dietary ascorbate (HDA), 50 mg/day, and low dietary ascorbate (LDA), 2 mg/day, for 21 weeks. Lenses from HDA animals were found to contain 3.3 times more ascorbate than LDA animals. Prior to irradiation, SDS-PAGE protein profiles and exopeptidase activity in HDA and LDA lens soluble proteins were indistinguishable. However upon exposure to UV light, more protein damage (e.g., high-molecular-weight aggregates and enhanced loss of exopeptidase activity) was seen in lens preparations from LDA as compared to HDA animals. These results suggest that ascorbate protects lens components against cataract-like and age-related postsynthetic changes in vivo. As in previous tests on lens preparations, attenuated exopeptidase activity was observed before protein aggregation.
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PMID:Delay of UV-induced eye lens protein damage in guinea pigs by dietary ascorbate. 329 91

Lenses of rats maintained on a 50% galactose diet displayed the development of a progressive cataract which was cortical at 3-11 days, and progressively internalized (nuclear as well) and mature at 16-20 days of feeding. Lens fiber plasma membranes were isolated from female rats subjected to the galactose diet and from controls at 11, 19, and 31 days of feeding, and analyzed by SDS-PAGE. Examination of the fiber plasma membranes from whole lenses of galactose-fed rats demonstrated the limited proteolysis of MP26 into MP23-24, in both the cortical and mature stages of the resultant cataracts. The limited proteolysis of MP26 was first evident in the lens cortex at 11 days of galactose feeding, and was evident as well, and more severe in proportion, in the lens nucleus at 19 days of feeding. The greatest proportion in MP26 limited proteolysis was observed in whole lenses at 31 days of galactose feeding. The regional progression of MP26 limited proteolysis closely paralleled the morphological progression of the galactose-induced cataract in the rat. The proportion of lens MP26 which underwent limited proteolysis into MP23-24 increased the longer the animals were kept on the galactose diet.
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PMID:Limited proteolysis of MP26 in lens fiber plasma membranes of the galactose-induced cataract in the rat. 353 34

Because of minimal or no turnover, lens proteins are subjected to substantial post-translational modifications which in turn disrupt lens architecture and change the optical properties leading to senile cataract formation. Progressive glycation is believed to have the potential to initiate the changes that are conducive to lens opacification. Fisher 344 rats were systematically followed from juvenile to older and aged phases of their life to study the relationship between lens glycation and high molecular weight (HMW) aggregate formation as well as quantitative and qualitative changes in lens crystallins. Levels of glycated proteins were quantified by affinity chromatography. Changes in lens crystallin composition and HMW aggregate formation were monitored by molecular sieve HPLC, further confirmed by SDS-PAGE and IEF techniques. As the age advances HMW and insoluble proteins increase with a concomitant disappearance of gamma-crystallins from soluble fraction. This disappearance of gamma-crystallins coincided with increased glycation (approximately 2-fold higher in insoluble fraction) and decreased sulfhydryl groups from soluble fraction. It appears that lens protein glycation, disappearance of gamma-crystallins and sulfhydryls from soluble fraction and increase of insoluble fraction and HMW aggregate are interrelated.
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PMID:Lens protein composition, glycation and high molecular weight aggregation in aging rats. 365 42

Intumescent cataractous lenses were investigated as to their water content and protein composition. Nuclei were separated from cortices. Water-soluble, water-insoluble, urea-soluble and urea-insoluble portions were quantified and the subunit composition of the water-soluble crystallin fraction was looked at on SDS-gel electrophoresis. Compared to normal lenses it is observed that the water content in intumescent cataract is increased, water-soluble and urea-soluble fractions are diminished, whereas the urea-insoluble portions are augmented. No major changes are noted in the subunit composition of the soluble protein fractions. Particularly, the relative amount of gamma-crystallins is diminished in intumescent cataractous lenses.
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PMID:Lens proteins in intumescent cataract. 373 13

The cytoskeletal pattern of the most superficial layers (cortex and epithelium) of senile cataractous lenses has been analyzed by PAGE-SDS. While the nuclear type of cataract and age-matched transparent human lenses have superimposable protein patterns, lenses with cortical cataract demonstrate appreciable modifications of their cytoskeletal composition. The most evident change is the decrease of fodrin and the marked reduction or even the absence of the 98 Kd band. Fodrin may be completely removed from the water insoluble fraction (WIF) of cortical cataract by extraction in low ionic strength buffer, a treatment which only partially solubilizes this protein in transparent control lenses.
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PMID:Cytoskeleton abnormalities in human senile cataract. 380 94

Quantification and biosynthesis of type I and type III collagens were determined in skin of control and Fraser mice (CatFraser mutation), which exhibit a genetically determined cataract. Skin organ cultures were labelled with [3H]proline. Pepsin-solubilized collagens were studied using three different approaches: (a) differential salt precipitation at neutral pH, followed by SDS-polyacrylamide gel electrophoresis; (b) differential salt precipitation at acid pH followed by SDS-polyacrylamide gel electrophoresis. (c) CNBr peptide analysis. These methods gave consistent and reproducible results, indicating a selective decrease of type I collagen in Fraser mouse skin as compared to control mouse skin. Metabolic labelling of skin organ cultures showed a decreased specific radioactivity of hydroxy[3H]proline in type I collagen of Fraser mouse skin. The concordant results of these experiments suggest a genetically determined alteration of interstitial collagen metabolism in the Fraser mutation apparently specifically concerning the expression of type I collagen gene(s).
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PMID:Selective decrease of type I collagen synthesis in Fraser mice skin. 393 69

The lens crystallins were analyzed in normal dogs and Miniature offSchnauzer dogs with congenital cataract formation. There was an increase in the relative proportions of alpha and beta L-crystallin and a decrease in the beta H and gamma-crystallin with increasing age in the noncataractous lens. These trends were advanced in the age-matched cataractous lenses. "Advanced aging" trends were also noted in various polypeptide components of beta-crystallin. Specifically, the appearance of a 29K band as well as a reversal of the 26K to 27.6K ratio occurred at an earlier age in the cataractous lens than in the clear lens. Three subunits of approximately 19K, 20K, and 21.5K were present on SDS-PAGE for alpha-crystallin from the cataractous lens as opposed to only two of 19K and 21.5K from the clear lens. However, if the protein was not heated following resolubilization in buffer containing 2% SDS and 5% 2-mercaptoethanol, only two subunits of 20K and 21.5K were evident in both clear and cataractous lenses. The electrophoretic behavior observed for both alpha and gamma-crystallins did not appear to be age related.
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PMID:Isolation and characterization of the crystallins of the normal and cataractous canine lens. 646 67

In vitro experiments were performed in order to understand the biochemistry of tryptophan-deficient cataract. Eleven-day-old embryonic chick lenses were cultured in vitro for 3 hr, one and three days in a tryptophan-deficient medium. DNA breakage was followed on sucrose gradient and water-soluble protein synthesis was analysed by SDS-PAGE coupled with fluorography. A medium lacking tryptophan delays the DNA degradation and decreases the synthesis of all soluble proteins including the crystallins.
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PMID:Changes in the DNA breakage and crystallin synthesis of embryonic chicken lenses cultured in a tryptophan-deficient medium. 670 42

Lens epithelium from patients with cataract was obtained during surgery and frozen. The samples were subjected to SDS-electrophoresis and Western blotting. Calpains were quantified using polyclonal antibodies against m- and mu-Calpain could be detected but not the isoenzyme mu-calpain, indicating that m-calpain is the significant most important calpain in human lens epithelium. Quantification of m-calpain showed no relationship to age or gender, but there were significant differences between different types of cataract.
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PMID:Calpains in lens epithelium from patients with cataract. 782 81

Methylglyoxal is an endogenous metabolite that increases in diabetes and has been implicated in some of its long-term complications such as retinopathy, neuropathy and cataract. We investigated the reaction of methylglyoxal with isolated human and bovine lens crystallins (alpha, beta H, beta L and gamma). After 7 days incubation at 37 degrees C and pH 6.9, the reaction of methylglyoxal with lens proteins yielded stable adducts that exhibited fluorescent properties. SDS-polyacrylamide gel electrophoresis was used to monitor aggregation and crosslinking of the modified protein and autoradiography showed that [14C]methylglyoxal was incorporated into all the protein bands. Bovine gamma-crystallin was the most reactive towards methylglyoxal. Reaction of methylglyoxal with bovine gamma II-crystallin, which is found mainly in the lens nucleus, could alter the change surface network of the molecule, resulting in aggregation, increased light scattering and hence cataract. Modification of gamma II-crystallin by methylglyoxal produced an overall loss of positive charge and an increase in molecular weight and non-disulfide covalent crosslinking. Amino acid analysis of the modified gamma II-crystallin showed a loss of 47% of arginine residues.
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PMID:The reaction of methylglyoxal with human and bovine lens proteins. 782 33


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