UMLS:C0086543 - FACTA Search

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Query: UMLS:C0086543 (cataract)
29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of lens in Ca2+-containing media, considered by several investigators to be a useful model of cataract formation, gave rise to significant alterations in the covalent structures of various proteins. In rabbit lens, when sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used after reduction of disulfides in urea, the most readily observable changes were (i) disappearance of 210K, 95K, and 60K proteins, (ii) modifications of alpha crystallin subunits, (iii) alterations of beta H crystallins, and (iv) de novo production of 55K and higher molecular weight polymers. The addition of leupeptin inhibited the disappearances of 210K, 95K, and 60K proteins and the alteration of alpha crystallins, suggesting that all these were caused by a Ca2+-activated protease. The proteolytically sensitive 60K species was identified as vimentin, a component of intermediate filaments. Formation of the 55K material and of higher molecular weight polymers during Ca2+ treatment of the lens could be prevented by histamine, a compound known to inhibit the transglutaminase-mediated cross-linking of proteins by epsilon-(gamma-glutamyl)lysine peptide bonds in other biological systems. It could also be shown by immunoblotting that an antibody raised against the 55K material reacted selectively with beta crystallins of normal lens. This indicates that the 55K product is in all likelihood an essential intermediate toward higher polymers and that the 55K product is a cross-linked dimer of certain polypeptides of beta crystallin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Formation of a 55 000-weight cross-linked beta crystallin dimer in the Ca2+-treated lens. A model for cataract. 398 92

To determine the influence of wide variations in dietary levels of calcium, zinc and phytic acid (as sodium phytate) on growth and cataract incidence, juvenile chinook salmon held at 10-11 degrees C were fed daily to satiation for 105 d one of nine purified diets containing one of three levels (grams/kilogram) of calcium (averaged 4.8, 17.7, 50.2), zinc (averaged 0.05, 0.15, 0.39) and phytic acid (1.62, 6.46, 25.8). Diets were formulated to have a calcium-phosphorus ratio of close to unity when considering phosphorus sources other than sodium phytate. High dietary phytic acid concentration (25.8 g/kg) depressed chinook salmon growth, food and protein conversion [protein efficiency ratio (PER)] and thyroid function, increased mortality, promoted cataract formation (zinc at 0.05 g/kg) and induced anomalies in pyloric cecal structure. Calcium at 51 g/kg (or phosphorus) exacerbated the effects of high dietary phytate and low dietary zinc on cataract incidence. Moreover, high dietary levels of calcium (48-51 g/kg) coupled with phosphorus significantly impaired the growth and appetite of low phytic acid (1.62 g/kg) groups and led to nephrocalcinosis in low and high phytic acid groups. Plasma zinc levels were directly related to dietary zinc concentration and inversely related to dietary phytic acid level. Calcium (51 g/kg) and/or phosphorus reduced zinc bioavailability when the diet concurrently contained 0.05 g zinc and 25.8 g of phytic acid per kilogram. It is concluded that zinc is essential for normal eye development in juvenile chinook salmon. Further, zinc deficiency could not be induced in chinook salmon fed diets with high ratios of calcium (or phosphorus) to zinc alone. This required the simultaneous presence of a strong mineral (zinc)-binding agent.
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PMID:Influence of dietary calcium, phosphorus, zinc and sodium phytate level on cataract incidence, growth and histopathology in juvenile chinook salmon (Oncorhynchus tshawytscha). 399 57

In the bovine lens the gamma IV-crystallin fraction is a principal determinant of the phase separation and opacification temperature, Tc (Siezen et al, Proc. Natl. Acad. Sci. USA 82, 1985, 1701). We have now measured the effect on Tc of purified gamma IV-crystallin solutions produced by a variety of reagents which affect protein-protein, protein-water and water-water interactions. Ionic strengths less than physiological increase Tc dramatically, while higher ionic strength has very little effect. Calcium ion concentrations up to 8 mM produce no change in Tc. Glycerol and acrylamide both depress Tc linearly with reagent concentrations; Tc depression of gamma IV-crystallin by these compounds is quantitatively the same as for whole lens. Sulfhydryl reducing agents such as glutathione and dithiothreitol lower Tc, while hydrogen peroxide increases Tc. Changes in opacification temperature of gamma IV-crystallin produced by oxidizing and reducing agents are time-dependent and highly non-linear with reagent concentration. Our results clearly show that bovine gamma IV-crystallin is an important target protein for various reagents which are known perturbants of the opacification temperature of whole lens. The relevance of these findings to human diabetic and senile cataract formation is discussed.
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PMID:Controlled modulation of the phase separation and opacification temperature of purified bovine gamma IV-crystallin. 406 30

Calcium has long been known to play a role in cataract formation but techniques have only recently become available for investigating the physiological mechanisms. Previous studies showed that lens membrane permeability alters when the external calcium concentration falls below 1 mM, so it was interesting that values for human aqueous from cataract patients ranged from 0.45 to 2.0 mM. The mean value for the aqueous was one half that for the plasma. The calcium concentration in cataractous lenses ranged from 0.1 to 64 mM and lenses with a high calcium concentration also had a high sodium content. In lenses with near normal sodium content the highest calcium concentrations were associated with highly localized opacities, while nuclear cataracts had a low calcium content. The relationship between calcium and transparency was investigated in a rat lens system using ion-sensitive microelectrodes. The distribution of free calcium in the lens varied with age and was correlated with a change in the sensitivity of the lens to cold cataract and a change in lens birefringence. The highest free calcium levels were obtained from lenses incubated in 10 mM-calcium in the absence of glucose and these lenses showed most light scattering. Ion-sensitive microelectrode techniques applied to human lenses yielded calcium levels of 0.1 microM-2 mM. In lenses with dense, highly localized opacities the calcium distribution was not uniform and was highest in regions that scattered most light. The movement of calcium through individual membrane channels was investigated using patch clamp techniques. Three types of ionic channels have been identified in the lens. The smallest appears to be a calcium channel; the larger current fluctuations are associated with sodium and potassium movements. In organ culture studies of the bovine lens, a marked decrease in protein synthesis and net leakage of proteins was associated more strongly with an increase in calcium than with an increase in sodium. The stability of the lens protein gel thus seems to depend on maintaining a low internal level of calcium ions.
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PMID:Calcium and the physiology of cataract. 609 95

A protein polymer characteristically present in human cataract was shown to contain significant amounts of gamma-glutamyl-epsilon-lysine isopeptides. It is proposed that these crosslinks are produced by the action of transglutaminase (R-glutaminyl-peptide:amine-gamma-glutamyl-yltransferase, EC 2.3.2.13), which is all the more plausible because lens contains the enzyme and endogenous protein substrates for it. The enzyme is similar to that obtained from liver and is Ca2+ dependent. Highest apparent activity is found in lens cortex. When cortex homogenate from the rabbit was incubated in the presence of Ca2+ with either [14C]putrescine or with dansylcadaverine, a a selective incorporation of the radioactive or fluorescent amine into the heavier subunits (Mr approximately 26,000 and 30,000) of beta-crystallins could be demonstrated. Possible modes of regulating the crosslinking activity of this enzyme in lens are discussed.
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PMID:Lens transglutaminase and cataract formation. 611 45

The present study was designed to examine the possible role of calcium in the opacification of x-ray-induced cataract in rabbit. The results demonstrate that the concentration of calcium in x-rayed lenses, just prior to lens hydration (7.5 weeks postirradiation), was twice that present in contralateral control lenses. At this stage of immature cataract, the lens nucleus remained transparent and maintained a normal level of calcium, but the lens cortex, containing regions of subcapsular opacification, accumulated a level of calcium that was twice that of the control. In the completely opaque mature cataract, (8-9 weeks postx-ray), both the cortex and nucleus had gained significant amounts of calcium. As the concentration of total calcium increased in the immature x-ray cataract, the amount of the cation bound to membranes and insoluble proteins of the cytosol also increased comparably. However, the relative proportion of calcium in the various fractions remained unaltered in the immature cataract; in both control lenses and immature cataracts, 20% of the total calcium remained in the membrane pellet and 70% was located in the soluble protein fraction. Only in the mature stage of cataract was a shift in the distribution of calcium apparent, as the proportion of calcium in the soluble protein fraction increased to 90%. Although only 7% of the total calcium in a mature cataract was bound to membrane, the amount represented a fivefold increase over the control. The results of this study demonstrate that an elevation in lens calcium accompanies the opacification process in x-ray cataract. The work also suggests that changes in calcium levels are not likely to result from inactivation of Ca-ATPase.
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PMID:Changes in the distribution of lens calcium during development of x-ray cataract. 622 54

The partial purification of (Na+ + K+)-ATPase from pig lens has been achieved by treatment with deoxycholate followed by density gradient centrifugation. The specific activity of the final preparation, ranging from 300 to 500 nmol/h per mg protein, is increased approx. 100-fold compared to the homogenate. A parallel increase in rho-nitrophenylphosphatase activity is also observed. Sodium dodecyl sulfate (SDS) gel electrophoresis reveals six major protein bands, one of which is the 93 kDa alpha subunit of (Na+ + K+)-ATPase which can be phosphorylated by reaction with [gamma-32P]ATP. A second band contains a glycoprotein which displays an apparent molecular weight of 51000 and thus appears to be the beta subunit of the enzyme. The enzyme is sensitive to ouabain with the I50 for (Na+ + K+)-ATPase and rho-nitrophenylphosphatase inhibition being 1.2 and 1.3 microM, respectively. Several agents which inhibit (Na+ + K+)-ATPase from other tissues such as oligomycin, Ca2+, vanadate, N-ethylmaleimide, rho-chloromercuribenzenesulfonic acid (PCMBS) and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) also inhibit the lens enzyme. Monovalent cations other than K+ are partially effective in activating the (Na+ + K+)-ATPase and rho-nitrophenylphosphatase activities. The K+ congeners were relatively more effective in supporting (Na+ + K+)-ATPase compared to rho-nitrophenylphosphatase activity. Other kinetic properties of the lens enzyme are also comparable to those of the enzyme from other tissues. Utilizing the partially purified membrane bound enzyme, discontinuities in Arrhenius plots of (Na+ + K+)-ATPase activity, rho-nitrophenylphosphatase activity and fluorescence polarization of the fluidity probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), are observed near the physiological temperature of lens. The possible significance of these observations for the mechanism of cataract formation are discussed.
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PMID:Characterization of partially purified (Na+ + K+)-ATPase from porcine lens. 629 83

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

We have investigated the ability of Ca2+ to induce the formation of high molecular weight (HMW) proteins in the intact lens. Ca2+ cataracts were produced in rabbit lenses by culturing the lenses for either four days in medium containing 20 mM Ca2+ or for three days in medium containing 100 mM Ca2+. Lenses cultured in 20 and 100 mM Ca2+ medium became opaque after 20 hr and contained 30 and 200 times higher levels of Ca2+, respectively, than transparent lenses cultured in medium containing 1 mM Ca2+. Lenses exposed to 100 mM Mg2+ did not lose transparency. The opacification of the lenses extended to a depth of 1 mm into the cortical layer and did not involve the nucleus. No significant differences were found in the concentrations of either soluble or insoluble proteins present in freshly excised lenses and Ca2+ cataracts. Soluble HMW proteins, greater than 1.5 X 10(6) daltons, were in two- and five-fold greater amounts in the 20 and 100 mM Ca2+ cataracts, respectively, compared to controls. HMW protein present in the 100 mM Ca2+ cataract amounted to approximately 3% of the total soluble protein in the lens. The amount of Ca2+ present in the HMW fraction was 1 Ca2+ per 5 X 10(5) daltons, no higher than that present in the unaggregated crystallins. No evidence was found for covalent bonding in the aggregate. Results of polyacrylamide gel electrophoresis and double immunodiffusion indicated the presence of alpha- and beta- but not gamma-crystallin in the HMW protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium-induced high molecular weight proteins in the intact rabbit lens. 643 38

We studied 62 eyes submitted to the Armed Forces Institute of Pathology (AFIP) from 1958 through 1980 that satisfied our criteria for the histologic diagnosis of Coats' disease. Our histopathologic definition of Coats' disease was the presence of a primary vascular lesion consisting of retinal telangiectasia with leakage of plasma to form intraretinal and subretinal exudates. In the cases we reviewed, Coats' disease occurred more frequently in boys, it usually affected only one eye, and was generally detected in the first decade of life. In 52 cases (79%) the clinical manifestations, strabismus and leukokoria, were thought to be caused by retinoblastoma. Angle closure glaucoma was present in 36 cases (58%). In all but one of the cases studied, the lesion was located peripheral to the equator. We further identified diffuse involvement of capillaries in the peripheral retina using trypsin-digest preparations. Associated histologic findings included: rubeosis iridis, cataract, vitreous neovascularization, and nodules resulting from fibrous metaplasia of the retinal pigment epithelium. These fibrous nodules typically occurred in the macular area and occasionally contained calcium or bone.
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PMID:Coats' disease: a study of 62 histologically confirmed cases. 650 5

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