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)

The Philly mouse is a new model for genetic cataracts, in which there is an apparent defect in lens membrane permeability. This abnormality results in electrolyte imbalance and lens hydration, typical of an osmotic cataract. Since membrane glycoproteins are believed to be involved in transport processes, we have studied the changes in these polypeptides in the Philly mouse lens during cataract development and compared them with those in the control Swiss-Webster mouse. The membrane glycoproteins were labeled by treatment with galactose oxidase and tritiated borohydride. Radioactivity was found to be incorporated into six glycoproteins of approximate molecular weights of 128 k, 103 k, 82 k, 71 k, 35 k, and 22 k daltons. The 35 k polypeptide is the major glycoprotein in the mouse lens membrane and shows increased incorporation of the tritium label with progression of the cataract. In contrast to the murine lens, the 35 k peptide could not be detected in rabbit lens membranes. Other changes observed in glycoproteins of the Philly mouse lens during cataract development were a loss of the 103 k and 71 k polypeptides and a corresponding increase in the 66 k polypeptide. These changes in glycoproteins may be related to the permeability changes and cataract development in the Philly mouse lens.
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PMID:Membrane glycoproteins of Philly mouse lens. 688 17

The anterior cortical fiber cells of the 12-day-old Nakano mouse lens revealed an extremely large number of gap junctions, the appearance of which was identical to those of the normal lens. Although the number of gap junctions of the cells in the same area at 29 days was comparable to that seen at 12 days, the size of each junction became smaller with cataract formation. The junctions were almost absent in the anterior cortical cells in 7-month-old Nakano mice. Biochemical analysis revealed that the 26,000 MW polypeptide closely associated with the cell membrane was lower in amount in the membrane preparation of the 29-day Nakano mouse lens than in the 12-day lenses. With the membrane fractions of lenses from 90-day Nakano mice, the absence of a major 26,000 NW polypeptide component correlates with the decrease in gap junction structures. The alternations in the gap junctions and membrane associated polypeptides of the Nakano lens may be linked with the steps leading to cataract development.
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PMID:Membrane alterations during cataract development in the Nakano mouse lens. 738 Jun 22

The pathophysiological events leading to cellular proliferation in proliferative vitreoretinopathy are largely unknown. An involvement of neuropeptides in that disease has recently been discussed, as substance P was found to be highly enriched in the intraocular fluid of patients with proliferative vitreoretinopathy. In the present study, aqueous humor was analyzed for another neuropeptide, vasoactive intestinal polypeptide. Radioimmunoassay revealed significantly increased levels of that polypeptide in the aqueous humor of patients with proliferative vitreoretinopathy as compared with cataract patients who served as controls. As vasoactive intestinal polypeptide contributes to the environment of the retinal pigment epithelial cell layer and induces proliferation of these cells in vitro, this peptide may be involved in the pathogenetic mechanisms leading to cellular proliferation in proliferative vitreoretinopathy.
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PMID:Different concentrations of vasoactive intestinal polypeptide in aqueous humor of patients with proliferative vitreoretinopathy and cataract patients. 780 11

The total proteins, water--soluble proteins and the urea--soluble proteins of the lens from fetal, adult and senile cataract were determined by SDS--PAGE. It was found that there was a 43KD polypeptide in the capsular--epithelium of all lens stated above. The band on SDS-PAGE corresponding to 43KD polypeptide was wide in the water--soluble proteins of the cortex and nucleus of the lenses obtained from over 14-year-old individuals. It became blurred in the urea--soluble proteins of cortex and nucleus of lens with aging, whereas it became almost disappeared in the senile cataract lens.
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PMID:[The 43KD polypeptide in the proteins of human lens]. 795 52

Proteolytic modifications of specific water soluble lens crystallins during U18666A cataract formation in young rats were identified by two dimensional gel electrophoresis and contrasted with those produced by incubating control lens homogenates with calcium. Protein changes which began in clear precataractous lenses at 12 days age included a decrease in 31 and 27 kDa (likely to be beta B1a and beta A3, respectively) crystallin polypeptides, increase in 25 kDa basic polypeptide, appearance of new polypeptide at 30 kDa and modification of alpha A-crystallin. Further modification of both alpha- and beta-crystallins occurred as cataracts formed; they progressed from early to advanced stage within a span of 4 days. During this period polypeptides beta B1a and beta A3 almost completely disappeared and several new components of 23-26 kDa in beta-crystallin region appeared. Extensive modification of alpha A resulted in appearance of new components of less than 20 kDa. Most of the gamma-crystallins disappeared from the water soluble proteins in advanced cataract lenses of 18 day old rats presumably by leaking out of the lens. The water insoluble proteins which accumulated in the cataract were very similar to modified crystallins which appeared in the water soluble fraction. In vitro incubation of normal lens water soluble proteins with calcium duplicated most of the protein changes seen during cataract progression. Immunoblotting studies with antisera to rat alpha- and beta-crystallins revealed the identity of most of the modified water soluble proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium activated proteolysis and protein modification in the U18666A cataract. 815 25

The purpose of these experiments was to examine the relationship between oxidation cataract and proteolysis in cultured rat lens. Hydrogen peroxide cataract showed insolubilization of protein, loss of 31 kDa beta B1-crystallin polypeptide, decreases in soluble calpain, and increases in insoluble calpain. This suggested that calpain may be activated in hydrogen peroxide treated lenses, since beta B1 is a known calpain substrate, and calpain undergoes autolysis and degradation when activated. Furthermore, the cysteine protease inhibitor E64 was partially effective in preventing development of H2O2-cataract. E64 also prevented the loss of the 31 kDa beta B1-crystallin polypeptide and decreased the loss of calpain in the lens. These results suggested that development of hydrogen peroxide induced cataract in rat lenses was associated with activation of calpain.
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PMID:Role of calpain in hydrogen peroxide induced cataract. 831 93

Age-related lens opacity is the major cause of loss of vision affecting more than half of the world's blind. The development of cataract is associated with changes in the structure of the lens. The lens consists largely of closely packed fibre cells forming a transparent syncytium. The main intrinsic polypeptide (MIP) of the lens fibre cells forms 40% of the fibre membrane, and forms a system of membrane channels. The precise structure and function of these channels remains obscure, although their role as large water-filled channels has been suggested in maintenance of structural integrity as well as their role in transport of nutrients. MIP is a member of a large family of channels of common ancestry. Some of the most recent studies of structure and function of this family have been carried out on CHIP (a water channel found in red blood cells) which is a member of this family closely related to MIP. Both CHIP and MIP m-RNA's have been expressed in oocyte membranes, and water permeabilities per channel have been measured. Surprisingly, CHIP and MIP channels have high and low water permeabilities, respectively. This is discussed in terms of recent high resolution structure determinations, the lens fibre MIP function, and future studies.
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PMID:Main intrinsic polypeptide and water movement--recent developments and future prospects. 872 70

delta 1-pyrroline-5-carboxylate synthetase (P5CS) catalyzes the ATP and the NAD(P)H-dependent conversion of L-glutamate to glutamic gamma-semialdehyde (GSA) which is the metabolic precursor for proline biosynthesis. We cloned a human P5CS cDNA by database cloning strategy and sequenced 2,907 bp from this cDNA which has a closed open reading frame (ORF) of 2,385 bp coding for a polypeptide of 795 amino acid residues. This cDNA, as its plant counterpart, encodes a bifunctional enzyme, with both gamma-glutamyl kinase (gamma-GK) and gamma-glutamyl phosphate reductase (gamma-GPR) activities that catalyzes the first 2 steps in proline biosynthesis and it hybridizes to a 4.5 kb mRNA from various tissues. A human genetic disease caused by a deficient P5CS has been recognized. The phenotypic features for deficiency of P5CS include joint hyperlaxity, skin hyperelasticity, cataract and mental retardation with hyperammonemia and low plasma levels of proline, citrulline and ornithine.
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PMID:Database cloning human delta 1-pyrroline-5-carboxylate synthetase (P5CS) cDNA: a bifunctional enzyme catalyzing the first 2 steps in proline biosynthesis. 876 62

The human RH locus appears to consist of two structural genes, D and CE, which map on the short arm p34-36 of chromosome 1 and specify a most complex system of blood-group genetic polymorphisms. Here we describe a family study of the Evans (also known as "D..") phenotype, a codominant trait associated with both qualitative and quantitative changes in D-antigen expression. A cataract-causing mutation was also inherited in this family and was apparently cotransmitted with Evans, suggesting a chromosomal linkage of these two otherwise unrelated traits. Southern blot analysis and allele-specific PCR showed the linkage of Evans with a SphI RFLP marker and the presence of a hybrid gene in the RH locus. To delineate the pattern of gene expression, the composition and structure of Rh-polypeptide transcripts were characterized by reverse transcriptase-PCR and nucleotide sequencing. This resulted in the identification of a novel Rh transcript expressed only in the Evans-positive erythroid cells. Sequence analysis showed that the transcript maintained a normal open reading frame but occurred as a CE-D-CE composite in which exons 2-6 of the CE gene were replaced by the homologous counterpart of the D gene. This hybrid gene was predicted to encode a CE-D-CE fusion protein whose surface expression correlates with the Evans phenotype. The mode and consequence of such a recombination event suggest the occurrence, in the RH locus, of a segmental DNA transfer via the mechanism of gene conversion.
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PMID:Genetic recombination at the human RH locus: a family study of the red-cell Evans phenotype reveals a transfer of exons 2-6 from the RHD to the RHCE gene. 880 97

Cataract induction in preweanling mice by L-buthionine sulfoximine (BSO), an inhibitor of glutathione biosynthesis, was correlated with perturbations in vitro protein biosynthesis. These were detected by incubation of late precataract and early cataract lenses with 35S-labeled amino acids, followed by dissection of lenses into capsule-epithelium and decapsulated fiber fractions, further processing of the fibers into water-soluble, urea-soluble and urea-insoluble fractions, and analysis by 2D electrophoresis and fluorography. Most of the protein labeling in control lenses was in the water-soluble fiber and capsule-epithelium fractions (80% and 14% of total cpm, respectively). Labeling in all three fiber fractions was decreased by cataract induction. The urea-insoluble fraction displayed a transient increase in labeled high molecular weight basic protein, as labeling of polypeptide monomers decreased. Densitometric analysis of fluorograms from the water-soluble and urea-soluble fiber fractions revealed a sharp decrease in fiber gamma-crystallin polypeptide labeling preceding and accompanying early cataract development, a delayed decrease in labeling of alpha A-crystallin and increased relative percentage of several labeled beta-crystallin polypeptides, especially in the urea-soluble fraction. By contrast with diminished labeling of the fiber fractions during cataract initiation, protein labeling of the corresponding capsule-epithelium fraction was stimulated dramatically and persisted at reduced levels during early opacification (stage 3), when nearly all of the protein labeling in the lens was found in capsule-epithelium. Capsule-epithelium polypeptides showing increased labeling during cataract initiation included alpha A-crystallin, several acidic polypeptides of M(r) = 40-50 kDa and a group of neutral to mildly acidic polypeptides of M(r) = 20-28 kDa. this transient activation, which was relatively non-specific, may relate to previously reported observations of polyribosome accumulation in lens epithelium during initial development of BSO cataracts. The labeled capsule-epithelium preparations are known to include newly differentiating fibers near the lens equator as well as epithelial cells. Both of these cell populations survive in mature BSO cataracts. It is suggested that modifications of the normal pattern of gene expression in the lens may be involved in initiation of the mouse BSO cataract and its subsequent pattern of development.
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PMID:Modifications in lens protein biosynthesis signal the initiation of cataracts induced by buthionine sulfoximine in mice. 894 43


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