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

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

Lipid extracts of the human cataractous and normal lenses were analyzed by thin-layer chromatography (TLC) using a solvent system consisting of CHCl3/CH3OH/CH3COOH/H2O (50:25:7:3 by vol.). A novel phospholipid having a Rf intermediate between phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS) was detected besides the four major phospholipids viz., PE, PS, phosphatidyl choline (PC) and sphingomyelin (SP). The novel phospholipid was found to be molybdenum positive and ninhydrin negative having a characteristic fluorescence of Schiff-base conjugate formed between PE, malondialdehyde (MDA) and PS. It was possible to resolve this adduct into PE and PS after acid hydrolysis using two dimensional TLC with CHCl3/CH3OH/NH3 (7 M) (65:25:4 by vol.) as the second solvent. In cataract PE . MDA . PS adduct increased significantly as did diene conjugates and MDA. In plasma membrane lipid extract of cataractous lenses there was a marked increase in fluorescence at 460 nm when excited at 365 nm showing a characteristic fluorescence of a typical Schiff-base conjugate. The evidence suggests that peroxidation of lenticular plasma membrane lipids is one of the molecular mechanisms involved in cataract in the human.
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PMID:Molecular mechanisms of cataractogenesis: IV. Evidence of phospholipid . malondialdehyde adduct in human senile cataract. 372 54

21 amino acids have been determined in aqueous humor obtained during microsurgical intraocular procedures in 30 patients with senile cataract and 27 patients with primary open-angle glaucoma. All individual amino acids showed higher levels in the glaucomas than in the cataracts: this is valid at 2p less than 0.05 for threonine, serine, asparagine, glutamine, methionine, tyrosine, phenylalanine, histidine, tryptophan, and arginine.
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PMID:Amino acid pattern in human aqueous humor of patients with senile cataract and primary open-angle glaucoma. 406 71

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 development of triparanol cataracts in rats is accompanied by the loss of lens (Na+ + K+)-ATPase activity and by alteration in the lens content and composition of phospholipids, sterols and phospholipid acyl groups. The lipid changes occur along the same time course as the loss of (NA+ + K+)-ATPase activity. Triparanol feeding produces a decrease in lens phospholipid content. The percentage contents of phosphatidylcholine and phosphatidyl-serine decrease while the content of sphingomyelin substantially increases. The amounts of oleic acid in lens phospholipids decrease while stearic and palmitic acids increase; however, these changes are relatively small. Sterol content is also decreased while the percentage content of desmosterol increases markedly. Feeding of the cataractogenic agents galactose and diazacholesterol also alters the lens lipid compositions and (Na+ + K+)-ATPase activity. A loss of phosphatidylserine is the only change in lipid properties which always accompanies a loss of the enzyme activity. The possible relationships between the lens content of phosphatidylserine, (Na+ + K+)-ATPase activity and the mechanism of triparanol-induced cataract formation are discussed.
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PMID:Lipid composition and (Na+ + K+)-ATPase activity in rat lens during triparanol-induced cataract formation. 626 59

Changes similar to posttranslational modifications that are observed with osmotic cataract formation in vivo can be seen with homogenates of lenses. These modifications are the loss of a 31,000 molecular weight (MW) beta crystallin polypeptide, an increase in a 25,000 MW membrane polypeptide. These modifications are potentiated by calcium and occur more rapidly at 37 degrees C than at 4 degrees C. Inhibitors of pepsin or of serine proteases do not influence these modifications, although proteolysis may be responsible for the changes observed.
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PMID:In vitro alterations similar to posttranslational modification of lens proteins. 669 42

The distribution of free amino acids and their related compounds has been determined in the aqueous humors of Wistar strain and Ihara cataract f-strain (ICR) aging rats. Taurine was the most abundant amino acid in aqueous humors except in ICR rats of 16 and 70 weeks. It was supposed that the increase of serine and glutamine, and the decrease of aspartate, proline and glycine in aqueous humors were related to aging. There were interesting changes in amino acids related to opacity of lens, concentration of taurine was lower than that of Wistar rats in ICR rats of 4, 16, and 70 weeks, alanine and citrulline increased in Wistar rats and decreased in ICR rats, and histidine increased in ICR rats with aging. The changes in free amino acids in aqueous humors were the greatest in ICR rats, and these data will provide useful clues for the formation of cataract and the transportation of amino acids.
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PMID:[Distribution of free amino acids and related compounds in ocular fluids of rat--I. Aging and inherited cataracts]. 778 8

Serine concentrations were markedly decreased in the cerebrospinal fluid of two brothers with congenital microcephaly, profound psychomotor retardation, hypertonia, epilepsy, growth retardation, and hypogonadism. The youngest boy also had congenital bilateral cataract. Magnetic resonance imaging of the brain showed evidence of dysmyelination. Plasma serine as well as plasma and cerebrospinal fluid glycine concentrations were also decreased but to a lesser extent. Treatment with oral serine in the youngest patient significantly increased cerebrospinal fluid serine and abolished the convulsions. In fibroblasts of both patients, a decreased activity was demonstrated of 3-phosphoglycerate dehydrogenase, the first step of serine biosynthesis (22% and 13% of the mean control value). This is an unusual disorder as the great majority of aminoacidopathies are catabolic defects. It is a severe but potentially treatable inborn error of metabolism that has not been previously reported in man.
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PMID:3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis. 875 34

CZP1, a locus for autosomal dominant "zonular pulverulent" cataract, previously had been linked with the Duffy blood-group-antigen locus on chromosome 1q. Here we report genetic refinement of the CZP1 locus and show that the underlying mutation is present in GJA8, the gene for connexin50. To map the CZP1 locus we performed linkage analysis using microsatellite markers on two distantly related branches of the original Ev. pedigree, which now spans eight generations. Significantly positive two-point LOD score (Z) values were obtained for markers D1S2669 (maximum Z [Zmax] = 4.52; maximum recombination frequency [thetamax] = 0) and D1S514 (Zmax = 4.48; thetamax = 0). Multipoint analysis gave Zmax = 5.22 (thetamax = 0) at marker D1S2669. Haplotyping indicated that CZP1 probably lies in the genetic interval D1S2746-(20.6 cM)-D1S2771. Sequence analysis of the entire protein-coding region of the GJA8 gene from the pedigree detected a C-->T transition in codon 88, which introduced a novel MnlI restriction-enzyme site that also cosegregated with the cataract. This missense mutation is predicted to result in the nonconservative substitution of serine for a phylogenetically conserved proline (P88S). These studies provide the first direct evidence that GJA8 plays a vital role in the maintenance of human lens transparency and identify the genetic defect believed to underlie the first inherited disease to be linked to a human autosome.
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PMID:A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q. 949 59


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