Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Packing interactions in the eye-lens. Structural analysis, internal symmetry and lattice interactions of bovine gamma IVa-crystallin. 273 25

Leakage of lens proteins from a hypermature cataract can result in a characteristic glaucoma that is associated with the invasion of the anterior chamber by monocytes. We hypothesized that the lens proteins themselves might account for the monocyte response. A sonicated lens induced concentration-dependent migration of monocytes in a Boyden chamber assay system. Checkerboard analysis indicated that the movement was directed rather than merely random. Relative to a control chemoattractant, N-formyl-methionyl-leucyl-phenylalanine, the lens induced monocyte migration more potently than neutrophil migration. The ability to induce migration was markedly reduced by incubating the lens with either trypsin or papain. Chemotactic activity was readily demonstrable in lenses from young donors without cataracts. Separation of lens proteins by gel filtration with high-performance liquid chromatography indicated that the chemotactic activity was most consistently associated with the gamma crystallin fraction. The chemotactic activity of lens proteins may contribute to the pathogenesis of phacolytic glaucoma or the uveitis resulting from retained cortical material after cataract extraction.
 ...
PMID:Chemotactic activity of lens proteins and the pathogenesis of phacolytic glaucoma. 367 92

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.
 ...
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.
 ...
PMID:Study of the relationship between free amino acids and cataract in human lenses. 614 81

With aging and cataract formation, modifications in absorption and fluorescence of the human lens proteins are observed. These changes have been investigated by the examination of the endopeptidase-resistant fraction isolated from human cataractous lenses. This fraction is highly enriched in atypical fluorescence and absorption (i.e. not attributable to tryptophan, tyrosine or phenylalanine). It has a molecular weight of approximately 3000, is enriched in acidic amino acids and has only a 280 nm shoulder in its u.v. spectrum. The material does not contain detectable levels of malondialdehyde or N-formylkynurenine. Upon acid hydrolysis the fluorescence and u.v. spectra remain unchanged with only a minor degree of cleavage observed. Structural studies on some of the cleavage products indicated the presence of oxindolyl alanine and kynurenine. These compounds could result from photo-oxidation of tryptophan.
 ...
PMID:The endopeptidase-resistant protein fraction from human cataractous lenses. 638 57

Female rats were fed defined diets limiting in one or more of certain amino acids and with or without vitamin E throughout gestation and lactation. Deficits of tryptophan, phenylalanine/tyrosine, or methionine/cystine reduced the body weight of progeny to about 50% or less of normal but only low tryptophan was cataractogenic. When total dietary amino acids were 12.4%, a low (65 mg%) level of tryptophan resulted in 34% incidence of cataract if vitamin E was simultaneously withheld. Elevation of total amino acids to 24.8% while maintaining tryptophan at 65 mg% caused 70 or 90% incidence of nuclear lens opacities in the presence or absence, respectively, of vitamin E. Maternal dietary amino acid imbalance was also associated with a 50% decrease in lens insoluble (membrane) proteins in the progeny independent of dietary vitamin E or the occurrence of opacities.
 ...
PMID:Cataract formation following limited amino acid intake during gestation and lactation. 646 60

Studies on the ultraviolet ray absorption in the aqueous humour of rabbit, cat, monkey, guinea pig, and rat showed marked species differences. In the rabbit aqueous the ascorbic acid, the proteins, and some amino acids (tyrosine, phenylalanine, cystine, and tryptophane) are together responsible for the total absorption, and a very great part of it refers to the ascorbic acid content. Accordingly, species with significant amounts of ascorbic acid in the aqueous (monkey, rabbit, guinea pig) have a greater absorption capacity towards ultraviolet radiation than species (cat, rat) lacking this substance. This effect of the ascorbic acid may contribute in protecting the lens against the most biotoxic ultraviolet rays. It seems that the ascorbic acid concentration is highest in the aqueous of typical day animals and lowest in species being active in the dark, indicating a correlation between the aqueous' ascorbic acid level and the quantity of incident light on the eye. The possible significance of changed aqueous ultraviolet ray absorption in the pathogenesis of human cataract development is discussed.
 ...
PMID:Aqueous humour and ultraviolet radiation. 677 94

The inducibility of glycosyl-phosphatidylinositol (GPI)-anchored proteins on affected paroxysmal nocturnal haemoglobinuria (PNH) neutrophils (PMN) after both in vitro and in vivo stimulation was investigated. Fc gamma R-III (CD16), decay-accelerating factor (DAF/CD55) and 20 kD homologous restriction factor (HRF20/CD59) were demonstrated to be concurrently deficient on unstimulated defective PNH PMN. Upon in vitro stimulation with either N-formyl-methionyl-leucyl-phenylalanine (fMLP), zymosan-activated serum (ZAS), or recombinant human granulocyte colony-stimulation factor (G-CSF), neither CD16 nor CD55 expression was induced on defective PNH PMN. G-CSF was administered to two patients with PNH when their conditions were complicated by bacterial infections, or to prevent infections associated with the extraction of teeth or cataract surgery. CD16 expression was induced on the defective PNH PMN in both cases during the administration of G-CSF, but the expression of CD55 and CD59 was not. CD16, induced on the defective PNH PMN during the administration of G-CSF, was phosphatidylinositol-specific phospholipase C (PIPLC)-sensitive, implying that it had GPI-linkage to the membranes. The patients treated with G-CSF recovered from infection or evaded infection. These observations suggest that a deficiency of GPI-anchored proteins is not always seen in defective PNH blood cells, at least under certain stimulation conditions.
 ...
PMID:Induction of Fc gamma R-III (CD16) expression on neutrophils affected by paroxysmal nocturnal haemoglobinuria by administration of granulocyte colony-stimulating factor. 769 30

Glycation is thought to be a factor in the development of cataract in elderly and diabetic patients. In this report, we describe our initial investigations on the reaction of the dipeptide glycyl-phenylalanine (GF) with different carbonyl compounds as a model of protein glycation. The results obtained demonstrate that the interaction of GF with carbohydrates has features in common with glycation of lens membrane proteins and lens crystallins.
 ...
PMID:Interaction of glycyl-phenylalanine with carbohydrates as a model of N-terminal glycation of proteins. 872 68

One of the major protein components of the ocular lens, alpha-crystallin, is composed of alphaA and alphaB chain subunits that have structural homology to the family of mammalian small heat shock proteins. Like other small heat shock proteins, alpha-crystallin subunits associate to form large oligomeric aggregates that express chaperone-like activity, as defined by the ability to suppress nonspecific aggregation of proteins destabilized by treatment with a variety of denaturants including heat, UV irradiation, and chemical modification. It has been proposed that age-related loss of sequences at the C terminus of the alphaA chain subunit may be a factor in the pathogenesis of cataract due to diminished capacity of the truncated crystallin to protect against nonspecific aggregation of lens proteins. To evaluate the functional consequences of alpha-crystallin modification, two mutant forms of alphaA subunits were prepared by site-directed mutagenesis. Like wild type (WT), aggregates of approximately 540 kDa were formed from a tryptophan-free alphaA mutant (W9F). When added in stoichiometric amounts, both WT and W9F subunits completely suppressed the heat-induced aggregation of aldose reductase. In contrast, subunits encoded by a truncation mutant in which the C-terminal 17 residues were deleted (R157STOP), despite having spectroscopic properties similar to WT, formed much larger aggregates with a marked reduction in chaperone-like activity. Similar results were observed when the chaperone-like activity was assessed through inhibition of gamma-crystallin aggregation induced by singlet oxygen. These results demonstrate that the structurally conservative substitution of Phe for Trp-9 has a negligible effect on the functional interaction of alphaA subunits, and that deletion of C-terminal sequences from the alphaA subunit results in substantial loss of chaperone-like activity, despite overall preservation of secondary structure.
 ...
PMID:Cloning, expression, and chaperone-like activity of human alphaA-crystallin. 894 44


1 2 3 Next >>