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)

A material with inhibitory action to Na+/K+ ATPase was found in the lens of the ICR/f rat, a recessive hereditary cataractous rat. The material also induced lens opacification in vitro. From the results of amino acid analysis and by secondary ion mass spectroscopy, it was suggested that the material might contain approximately equimolar amounts of four amino acids, ie, aspartic acid, serine, glutamic acid and glycine, and that the molecular weight was 444. These facts suggested that this material with Na+/K+ ATPase inhibitory action might be a peptide. However, there is not yet any corroborating evidence to show whether this peptide is only a single material or not. The peptide significantly increased with aging in the lens of the ICR/f rat until approximately 90 days, when cataract became manifest, but its content decreased thereafter. This study suggests that one of the causes of cataractogenesis in the ICR/f rat might be this peptide, which is transformed in the lens with aging, and also that the peptide might accelerate lens opacification after cataractogenesis.
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PMID:Characterization of peptide inducing cataractogenesis in lens of hereditary cataractous rat (ICR/f RAT). 255 1

There was a gradual decrease in the quantity of various amino acids associated with cataract formation due to reduced concentrations of glutamic acid, threonine, serine, glycine, alanine, leucine, isoleucine, phenylalanine and tyrosine in stages of cataract formation.
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PMID:Study of the relationship between free amino acids and cataract in human lenses. 614 81

The amino acids lysine and glycine are reported to react with glucose at physiological pH and temperature and undergo non-enzymic glycation. Three other amino acids present in relatively larger amounts in the lens i.e. alanine, aspartic acid and glutamic acid were also found to undergo non-enzymic glycation as found by incorporation of uniformly labelled (U-[14C]) glucose into the amino acids. The glucose incorporation was 1.6 to 2.5% for alanine, 35 to 50% for aspartic acid and 2.3 to 3.3% for glutamic acid. Each amino acid of varying concentrations lowered the extent of in vitro glycation of lens proteins significantly in glucose-treated homogenates of normal lens from humans. The decrease in glycation for alanine was between 32 and 69%, that for aspartate was between 18 and 74%, and for glutamate was between 52 to 74%. Decreased glycation was greater for higher concentrations of glucose. Scavenging of intracellular glucose and decreasing the extent of glycation of lens proteins could be the mechanism of action by which the amino acids alanine, aspartic acid and glutamic acid could exercise a beneficial effect on cataract and diabetic retinopathy.
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PMID:Free alanine, aspartic acid, or glutamic acid reduce the glycation of human lens proteins. 887 7

According to the World Health Organization, cataracts account for half of the blindness in the world, with the majority occurring in developing countries. A cataract is a clouding of the lens of the eye due to light scattering of precipitated lens proteins or aberrant cellular debris. The major proteins in the lens are crystallins, and they are extensively deamidated during aging and cataracts. Deamidation has been detected at the domain and monomer interfaces of several crystallins during aging. The purpose of this study was to determine the effects of two potential deamidation sites at the predicted interface of the betaA3-crystallin dimer on its structure and stability. The glutamine residues at the reported in vivo deamidation sites of Q180 in the C-terminal domain and at the homologous site Q85 in the N-terminal domain were substituted with glutamic acid residues by site-directed mutagenesis. Far-UV and near-UV circular dichroism spectroscopy indicated that there were subtle differences in the secondary structure and more notable differences in the tertiary structure of the mutant proteins compared to that of the wild type betaA3-crystallin. The Q85E/Q180E mutant also was more susceptible to enzymatic digestion, suggesting increased solvent accessibility. These structural changes in the deamidated mutants led to decreased stability during unfolding in urea and increased precipitation during heat denaturation. When simulating deamidation at both residues, there was a further decrease in stability and loss of cooperativity. However, multiangle-light scattering and quasi-elastic light scattering experiments showed that dimer formation was not disrupted, nor did higher-order oligomers form. These results suggest that introducing charges at the predicted domain interface in the betaA3 homodimer may contribute to the insolubilization of lens crystallins or favor other, more stable, crystallin subunit interactions.
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PMID:Deamidation alters the structure and decreases the stability of human lens betaA3-crystallin. 1761 72

Cataracts are a clinically diverse and genetically heterogeneous disorder of the crystalline lens and a leading cause of visual impairment. Here we report linkage of autosomal dominant "progressive childhood posterior subcapsular" cataracts segregating in a white family to short tandem repeat (STR) markers D20S847 (LOD score [Z] 5.50 at recombination fraction [theta] 0.0) and D20S195 (Z=3.65 at theta =0.0) on 20q, and identify a refined disease interval (rs2057262-(3.8 Mb)-rs1291139) by use of single-nucleotide polymorphism (SNP) markers. Mutation profiling of positional-candidate genes detected a heterozygous transversion (c.386A-->T) in exon 3 of the gene for chromatin modifying protein-4B (CHMP4B) that was predicted to result in the nonconservative substitution of a valine residue for a phylogenetically conserved aspartic acid residue at codon 129 (p.D129V). In addition, we have detected a heterozygous transition (c.481G-->A) in exon 3 of CHMP4B cosegregating with autosomal dominant posterior polar cataracts in a Japanese family that was predicted to result in the missense substitution of lysine for a conserved glutamic acid residue at codon 161 (p.E161K). Transfection studies of cultured cells revealed that a truncated form of recombinant D129V-CHMP4B had a different subcellular distribution than wild type and an increased capacity to inhibit release of virus-like particles from the cell surface, consistent with deleterious gain-of-function effects. These data provide the first evidence that CHMP4B, which encodes a key component of the endosome sorting complex required for the transport-III (ESCRT-III) system of mammalian cells, plays a vital role in the maintenance of lens transparency.
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PMID:CHMP4B, a novel gene for autosomal dominant cataracts linked to chromosome 20q. 1770 5

Connexin46 (Cx46), together with Cx50, forms gap junction channels between lens fibers and participates in the lens pump-leak system, which is essential for the homeostasis of this avascular organ. Mutations in Cx50 and Cx46 correlate with cataracts, but the functional relationship between the mutations and cataract formation is not always clear. Recently, it was found that a mutation at the third position of hCx46 that substituted an aspartic acid residue with a tyrosine residue (hCx46D3Y) caused an autosomal dominant zonular pulverulent cataract. We expressed EGFP-labeled hCx46wt and hCx46D3Y in HeLa cells and found that the mutation did not affect the formation of gap junction plaques. Dye transfer experiments using Lucifer Yellow (LY) and ethidium bromide (EthBr) showed an increased degree of dye coupling between the cell pairs expressing hCx46D3Y in comparison to the cell pairs expressing hCx46wt. In Xenopus oocytes, two-electrode voltage-clamp experiments revealed that hCx46wt formed voltage-sensitive hemichannels. This was not observed in the oocytes expressing hCx46D3Y. The replacement of the aspartic acid residue at the third position by another negatively charged residue, glutamic acid, to generate the mutant hCx46D3E, restored the voltage sensitivity of the resultant hemichannels. Moreover, HeLa cell pairs expressing hCx46D3E and hCx46wt showed a similar degree of dye coupling. These results indicate that the negatively charged aspartic acid residue at the third position of the N-terminus of hCx46 could be involved in the determination of the degree of metabolite cell-to-cell coupling and is essential for the voltage sensitivity of the hCx46 hemichannels.
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PMID:Cataract-associated D3Y mutation of human connexin46 (hCx46) increases the dye coupling of gap junction channels and suppresses the voltage sensitivity of hemichannels. 2284 97