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 Emory mouse is presumed to be a model for studies on human senile cataracts. The cataract develops in 5-8 months after birth, and it does not appear to have an osmotic component. To date, no specific metabolic lesion has been uncovered as a probable cause to this cataract. Several studies have shown that the Emory mouse undergoes accelerated aging changes, possibly leading to development of senile-type cataracts. In this study we quantitated changes that might occur in the population of various mRNAs for proteins presumed to be essential for lens transparency, and for proteins that may contribute to development of cataracts. By Northern blot hybridization analysis we quantitated the mRNAs for: alpha A-crystallin, beta B1-crystallin, gamma-crystallin, the main lens intrinsic membrane protein, MP26, and aldose reductase; all in lenses of Emory mouse early cataract strain (EMEC), and of an age-matched cataract resistant strain (CR). These measurements were done in increments of 1 month over a 6-month period, then at both 9 and 12 months. The results show that all of these mRNAs decrease with age and with development of cataracts; although in some cases the initial concentrations at 1 month appear to be lower in the EMEC than in the CR strain. The most dramatic change occurred with the MP26 mRNA. In the CR strain, MP26 mRNA maintained its high concentration for a period of about 6 months before it began its decline to the 12 month level (about 25% of the 1 month level).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Profile of messenger RNA decay in the Emory mouse lens in cataractogenesis and in aging. 148 8

The formation of membrane protein disulfide was investigated at various stages of development of X-ray-induced cataract in the rabbit. Intermolecular disulfide bonding of lens membrane proteins was detected not only in the mature cataract (occurring 8-9 weeks after the X-ray dose) but also at 1 week prior to maturation, in which no significant increase in lens hydration occurs and where opacification is confined mainly to the posterior subcapsular region. Two-dimensional diagonal electrophoresis revealed that polypeptides with apparent molecular weights of 21, 23, 25, 31, 35, 46 and 53 kilodaltons were involved in cross-linking. The MP26 membrane polypeptide was not significantly involved in the disulfide bonding. The oxidation of membrane proteins in stages other than mature was evident only in the lens nucleus (which remained clear) and not in the cortex. The results of this study indicate that an intermolecular disulfide linkage of cytosolic proteins to membranes occurs prior to formation of mature cataract, and may be a precursor to protein aggregation and insolubilization in the mature nuclear cataract.
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PMID:Disulfide-linked membrane proteins in X-ray-induced cataract. 365 24

Lens fiber proteins with apparent molecular weights 57,000, 70,000, 82,000, and 100,000 were components in urea insoluble, membrane-rich fractions. Monoclonal antibodies against these proteins labeled membranes by immunofluorescence microscopy of sheep lens cryosections and are thus referred to as membrane proteins MP57, MP70, MP82, and MP100. MP70 has previously been localized in fiber junctional membranes (Kistler et al 1985, J Cell Biol 101:28-35). Using radioimmunoassays, the authors found a different membrane protein composition for the cortical and nuclear sheep lens regions. In addition, the membrane protein composition altered with the overall lens age. All the above membrane antigens were eventually cleaved by proteolysis in older fibers, and their degradation patterns could be grouped into distinct classes. The results are of basic importance for cataract research.
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PMID:Aging of lens fibers. Mapping membrane proteins with monoclonal antibodies. 370 26

A single injection of 20 mumol sodium selenite/kg body weight in 10-day-old rats caused severe nuclear cataract within 4 days. By 4 days postselenite injection, nuclear calcium levels increased from 0.4 to 6.8 mmol/kg lens dry weight. The purpose of these experiments was to determine if this calcium increase was associated with proteolysis specifically in the lens nuclear region. Sodium dodecyl sulfate polyacrylamide electrophoresis of lens nuclear proteins following selenite injection showed: loss of 30, 27, and 26 K molecular weight polypeptides in the soluble fraction, loss of 83, 52, 30, 27, and 26 K polypeptides in the insoluble fraction, and loss of the major 26 K membrane protein. Gel chromatography of nuclear soluble proteins indicated a decrease in beta H and beta L crystallins following selenite injection. Two-hour in vitro incubation of nuclear lens homogenates with calcium duplicated many of the proteolytic changes occurring in lenses in vivo following selenite injection. Calcium induced proteolysis in vitro was inhibited by EGTA, leupeptin, and iodoacetate but was not inhibited by phenylmethylsulfonyl fluoride. These properties are similar to calcium activated protease (CAP) from other tissues. Activation of CAP, and subsequent degradation of nuclear proteins, may be causes of selenite cataract.
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PMID:Calcium-activated proteolysis in the lens nucleus during selenite cataractogenesis. 638 40

Biochemical evidence is presented for the disintegration of the lens fiber plasma membrane in human cataracts. The intrinsic membrane proteins are found in both the water-soluble and water-insoluble nonmembrane fractions of the cataract lens but not in the normal tissue. Furthermore, in contrast to the normal lens, not all of the lipid found in the cataractous lens is isolated with the membrane fraction. In cataracts, both the membrane and membrane fragments are involved in covalent high molecular weight aggregates with an extrinsic membrane protein (43,000 daltons) and a cytoplasmic protein (gamma-crystallin).
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PMID:Biochemical evidence for membrane disintegration in human cataracts. 678 60

Plasma membrane contains extrinsic as well as intrinsic proteins. Changes in the extrinsic proteins of lens membrane during human aging and cataract formation have not been investigated in detail. Unlike previous studies which examined lens membrane after being stripped of extrinsic proteins by treatment with chaotropic agents, we have isolated whole or 'native' lens membrane on a sucrose gradient by ultracentrifugation of the total water-insoluble protein. Essentially all of the water-insoluble protein from young to aged to cataractous human lens appeared membrane associated. In young lens (20-37 years old), most of the membrane banded at the 25/45% sucrose interface fraction. This fraction contained relatively little urea-soluble protein and likely represents fiber-cell plasma membrane with its physiologically associated extrinsic and intrinsic proteins. With aging (62-80 years old), about one-third of the membrane, as judged by the distribution of cholesterol, banded at a much higher density (50/58% sucrose fraction). The higher density was due to a great increase in the membrane's relative protein content (protein/cholesterol). Although this extra protein was composed of both urea-insoluble and -soluble fractions, the urea-soluble protein predominated in all lenses. Cataractous lens differed from aged-clear lens in that much more of the total membrane (70-75%) had shifted to the high density and participated in this massive binding of cytosolic proteins. Although alpha-crystallin was the principal extrinsic-membrane protein in young lens, high molecular weight aggregate of modified (acidic) crystallins accounted for the increased extrinsic protein in aging. The extrinsic proteins bound to both clear-aged and cataractous lens membrane were aggregated. In conclusion, examination of human lens native membrane fractions revealed that the association of crystallins with membrane in both aging and cataracts was much greater than previously recognized and most of this increased protein was non-covalently bound to the membrane. Much more of the lens total membrane from cataractous than clear-aged lens was involved in this massive protein association and the protein bound to cataract membrane appeared more highly aggregated.
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PMID:Protein associated with human lens 'native' membrane during aging and cataract formation. 764 53

The interaction of human and bovine alpha-crystallins with bovine lens membranes was evaluated using binding curves and Scatchard plots constructed from scans of SDS-PAGE gels and/or from the association of [14C]-leu alpha-crystallin with the membranes. No differences were observed for total bovine, normal human 19 and 88 year old and cataractous alpha-crystallins. In each case, interaction takes place through two distinct processes, a) a high affinity (Kd = 1 x 10(-8) M) binding with low capacity (25 mg alpha-crystallin/g membrane protein) and b) partitioning (Kp = 0.25 l/g membrane protein). Loss of the high-affinity binding component was observed for bovine nuclear alpha-crystallin. Contrary to previous reports, it is concluded that cataract formation does not affect the ability of human alpha-crystallins to interact with bovine lens membranes. Reanalysis of previously published data supports this conclusion.
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PMID:On the interaction of alpha-crystallin with membranes. 819 71

Four genes encoding eye lens-specific proteins, potential candidate genes for congenital cataract (CC) mutations, were mapped in the mouse genome using a panel of somatic cell hybrids and DNAs from the EU-CIB (European Collaborative Interspecific Backcross). Two of them are lens fiber cell structural proteins: the Cryba1 locus encoding crystallinbetaA3/A1 maps to chromosome 11, 2.5 +/- 2.5 cM distal to D11Mit31, and the Crybb2 locus encoding crystallinbetaB2 maps to chromosome 5, 9.1 +/- 4.3 cM distal to D5Mit88. The other two genes encode lens-specific gap junction and integral membrane proteins, respectively: The Gja8 locus encoding gap juction membrane channel protein alpha8, also called connexin50 or MP70, maps to chromosome 3, 11.9 +/- 5.0 cM distal to D3Mit22, and the Lim2 locus encoding lens intrinsic membrane protein 2, also called MP19, maps to chromosome 7, 2.5 +/- 2.5 cM proximal to Ngfg. All four map positions, when compared with the corresponding positions in human, lie within known regions of conserved synteny between mouse and human chromosomes.
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PMID:Mapping of four mouse genes encoding eye lens-specific structural, gap junction, and integral membrane proteins: Cryba1 (crystallin beta A3/A1), Crybb2 (crystallin beta B2), Gja8 (MP70), and Lim2 (MP19). 866 93

Many types of inherited early onset cataract are known in both human and mouse. Here we describe the mapping of two novel dominant cataract loci in the mouse genome. Cataract and curly whiskers, Ccw, maps to Chromosome 4, 3.1 +/- 1.1 cM distal to the b (brown) locus. Total opacity 3, To3, maps to Chromosome 7, 7.1 +/- 1.8 cM proximal to p (pink-eyed dilution). The map positions of two other dominant cataract mutants have now been refined by three-point crosses. Nuclear and posterior polar cataract, Npp, maps to the central part of Chromosome 5, 1.4 +/- 0.5 cM distal to We (dominant spotting-extreme, an allele at the Kit locus), and Opaque secondary fiber cell junctions, Opj, maps to the proximal region of Chromosome 16, 9.1 +/- 1.5 cM distal to the marker md (mahoganoid). While there are no obvious candidate genes in the vicinity of the Ccw, Npp, and Opj mutations, To3 lies remarkably close to the recently mapped Lim2 locus, which encodes lens intrinsic membrane protein 2, also called MP19.
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PMID:Two new cataract loci, Ccw and To3, and further mapping of the Npp and Opj cataracts in the mouse. 881 11

The purpose of this study was to evaluate the role of altered calcium homeostasis in the development of irreversible membrane damage in the UVB-irradiated ocular lens. In particular, experiments were designed to determine whether restricting calcium influx could prevent membrane damage that typically leads to ion imbalances and lens opacification following short-term exposure to ultraviolet light (UVB). The influx of calcium was reduced by culturing lenses in a low-calcium culture medium containing 0.3 mM Ca2+ rather than physiological concentrations of 1.6 mM. This low-calcium protocol retarded calcium accumulation in UVB-irradiated lenses for 2 days of culture, and opacification was delayed by 24 h. Loss of transparency did occur during the second day of culture, but more slowly than in irradiated lenses cultured in normal-calcium medium. Membrane damage was assessed by evaluating loss in cation transport activity, assessed by measuring 86Rb uptake into cultured lenses. Uptake was markedly inhibited in UVB-irradiated lenses and low-calcium culture did not prevent this inhibition of cation transport, a finding that explains why low-calcium protocol did not help maintain sodium homeostasis in irradiated lenses. Inhibition of cation transport and sodium accumulation eventually caused lens hydration and light scattering during extended culture in the absence of significant calcium elevation. Additional experiments were done to establish whether initial damage sustained by membranes could be repaired through the biosynthesis of new membrane proteins. Incorporation of 14C-histidine in membranes of the UVB-exposed lens was measured to assess membrane synthesis essential for repairing membrane damage. The rate of membrane protein synthesis, assessed by measuring incorporation of labeled amino acids, declined in UVB cataract, despite the prevention of calcium accumulation. These results suggest that one explanation for irreversible gain in sodium and calcium content accompanying opacification is the inability of lenses to replenish damaged membrane proteins comprising ion channels or transporters.
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PMID:The role of calcium in UVB-induced damage in irradiated ocular lenses. 906 96


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