Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

alphaA-crystallin is a small heat-shock protein expressed preferentially in the lens and is detected during the early stages of lens development. Recent work indicates that the expression of alphaA-crystallin enhances lens epithelial cell growth and resistance to stress conditions. Mutation of the arginine 116 residue to cysteine (R116C) in alphaA-crystallin has been associated with congenital cataracts in humans. However, the physiological consequences of this mutation have not been analyzed in lens epithelial cells. In the present study, we expressed wild type or R116C alphaA-crystallin in the human lens epithelial cell line HLE B-3. Immunofluorescence and confocal microscopy indicated that both wild type and R116C alphaA-crystallin were distributed mainly in the cytoplasm of lens epithelial cells. Size-exclusion chromatography indicated that the size of the alphaA-crystallin aggregate in lens epithelial cells increased from 500 to 600 kDa for the wild type protein to >2 MDa in the R116C mutant. When cells were exposed to physiological levels of UVA radiation, wild type alphaA-crystallin protected cells from apoptotic death as shown by annexin labeling and flow cytometric analysis, whereas the R116C mutant had a 4- to 10-fold lower protective ability. UVA-irradiated cells expressing the wild type protein had very low TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) staining, whereas cells expressing R116C mutant had a high level of TUNEL staining. F-actin was protected in UVA-treated cells expressing the wild type alphaA-crystallin but was either clumped around the apoptotic cells or was absent in apoptotic cells in cultures expressing the R116C mutant. Structural changes caused by the R116C mutation could be responsible for the reduced ability of the mutant to protect cells from stress. Our study shows that comparing the stress-induced apoptotic cell death is an effective way to compare the protective abilities of wild type and mutant alphaA-crystallin. We propose that the diminished protective ability of the R116C mutant in lens epithelial cells may contribute to the pathogenesis of cataract.
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PMID:The R116C mutation in alpha A-crystallin diminishes its protective ability against stress-induced lens epithelial cell apoptosis. 1175 14

The aim of the present work was to evaluate the effect of bendazac lysine on the human lens epithelial cell line HLE-B3 adhesion to polymethylmethacrylate (PMMA) intraocular lenses (IOLs). After adherence to IOLs, cells were incubated in the presence of the drug for 24 h. The number of cells contained in a 6-mm(2) area was then counted with an inverted phase microscope and adherent cells were distinguished from detached floating cells by focusing through the medium. Results obtained show that bendazac is able to induce a linear dose-dependent inhibition of HLE-B3 adhesiveness to PMMA IOLs. In particular, treatment with bendazac 33, 100 and 300 microM resulted in a 15, 32 and 54% inhibition, respectively. Statistical analysis shows that this effect is significant at 100 microM (p < 0.05) and 300 microM (p < 0.01). The analysis of the effects of bendazac on the viability and on the proliferative capacity of HLE-B3 cells did not show any drug-related toxicity up to the concentration of 400 microM. The present study demonstrates that bendazac lysine is able to inhibit adhesion of lens epithelial cells to PMMA IOLs and suggests the potential beneficial use of this drug in preventing secondary cataract development.
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PMID:Bendazac lysine inhibition of human lens epithelial cell adhesion to polymethylmethacrylate intraocular lenses. 1510 5

We investigated whether amyloid beta(Abeta) aggregates have transforming growth factor beta- like cytokine activity and cause transdifferentiation of lens epithelial cells, leading to certain types of cataract. In order to mimic Abetaaggregates, Abeta-(1-40) was crosslinked to bovine serum albumin (BSA) with disuccinimidyl suberate according to a previously described procedure. When human lens epithelial B-3 (HLE B-3) cells were treated with the Abeta-(1-40)-BSA conjugates, we observed the translocation of Smad-3, as well as the induced mRNA levels of fibronectin (FN), collagen type I (Col I), smooth muscle actin (SMA) and matrix metalloproteinase-2 (MMP-2). In addition, we investigated the morphology of rat whole lens cultured for 5 days in the presence of Abeta-(1-40)-BSA, and the immunohistochemical localizations of Abeta-(1-40)/amyloid precursor protein (APP) in human clinical tissues beneath the anterior capsules. In rat whole lens cultures, treatment with Abeta-(1-40)-BSA produced a transformed morphology that had multiple layers of lens epithelial cells. To compare the anterior capsules in anterior subcapsular cataracts with those in nuclear cataracts, immunohistochemical studies of Abeta/APP in human clinical tissues revealed that the predominant immunostaining of Abeta occurs in the anterior epithelial plaques, which likely produces the abnormal extracellular matrix. Thus, these findings suggest that Abeta aggregates in vivo are possibly involved in the regulatory process by which lens epithelial cells may transdifferentiate into fibroblast-like cells, as well as help understand the mechanisms which lead to certain types of cataractogenesis.
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PMID:Possible role of amyloid beta-(1-40)-BSA conjugates in transdifferentiation of lens epithelial cells. 1511 92

The focus of the study was to characterize plasma membrane calcium-ATPase pump (PMCA) isoform expression in the human lens and cultured lens epithelial cells as a basis for future studies of calcium homeostasis in the lens. Proteins and mRNA expression were analysed using Western Immunoblotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. Clear human lenses from the Kentucky Lions Eye Bank and an immortalized human lens epithelial cell line (HLE B-3) were used. RT-PCR products of PMCA1, PMCA2, and PMCA4 primers were detected at 429, 557, and 849bp, respectively. All these products were identified as PMCA isoforms by sequence analysis. Protein bands at approximately 130, 115, and 135kDa were detected by Western blot analysis for PMCA1, PMCA2 and PMCA4, respectively. PMCA3 was not detected at protein or mRNA level in any human lens sample or cell culture, but was detected in the rat brain cortex used as a control. Several bands with lower molecular weights, especially for PMCA2, were detected in the epithelial samples and probably represent break down products of PMCA2. No PMCA proteins or breakdown products were detected in the nuclear or cortical fractions from human lenses. PMCA1, 2, and 4 proteins and mRNAs are expressed in human lens epithelium and cultured epithelial cells; PMCA3 is not. PMCA was not detected at all in the lens fibre cells. The calcium pump must be selectively processed, independent of other membrane proteins such as the Na-K-ATPase pumps, because the distribution of the Na-K-ATPase pump is asymmetrical in the epithelium and present throughout the lens whereas the calcium pumps are not. The findings of this study provide a basis for further studies to examine the role and modulation of PMCA isoforms in calcium homeostasis and in the development of cataract.
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PMID:Plasma membrane Ca2+-ATPase expression in the human lens. 1597 55

Alterations of intracellular levels of myo-inositol (MI) have the potential to impact such cellular processes as signaling pathways and osmotic balance. Depletion of MI has been implicated in the etiology of diabetic complications; however, the mechanistic details remain sketchy. myo-Inositol oxygenase (MIOX-EC 1.13.99.1) catalyzes the first committed step of the only pathway of MI catabolism. In the present study, extra-renal tissues and cell types, including those affected by diabetic complications, were examined for MIOX expression. Western blotting results indicated that kidney is the only major organ where MIOX protein is expressed at detectable levels. Immunohistochemical examination of the kidney revealed that the proximal tubular epithelial cells are the only site of MIOX expression in the kidney. Reverse-transcription-polymerase chain reaction (RT-PCR) and Western immunoblot analyses, however, revealed that the cell lines ARPE-19 and HLE-B3, representing human retinal pigmented epithelium and lens epithelium, respectively, also express MIOX. In addition, quantitative real-time RT-PCR analysis of all major tissues in the mouse showed that the sciatic nerve contained MIOX transcript, which was found to be significantly higher than that observed in other non-renal organs. These results indicate that MIOX is found at lower levels in extra-renal tissues where diabetic complications, including nephropathy, neuropathy, retinopathy, and cataract, are frequently observed.
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PMID:Expression of myo-inositol oxygenase in tissues susceptible to diabetic complications. 1633 55

1-cys peroxiredoxin (1-cysPrx), a member of the peroxiredoxin family with a single conserved cysteine residue, reduces a broad spectrum of hydroperoxides. This study was undertaken to examine changes in 1-cysPrx expression in human cataract samples, human lens epithelial (HLE B3) cell line, and rat organ-cultured lenses in response to oxidative insult induced by H2O2 or transforming growth factor-beta1 (TGF-beta1). Expression of 1-cysPrx mRNA and protein in HLE B3 cells increased in response to 2-8 ng ml(-1) TGF-beta1 and 50-75 microm H2O2 and then decreased below the control level at high doses (10 ng ml(-1) TGF-beta1 and 100-150 microm H2O2), as determined by Northern blot and immunoblot analysis. This reduction coincided with the decrease of cell viability. Immunoreactive 1-cysPrx protein was measured in capsulorrhexis specimens obtained from patients with anterior subcapsular cataract (ASC), nuclear sclerosis (NS), cortical spokes (CS), posterior subcapsular cataract (PSC), or white mature cataract (WC) at the time of cataract surgery. Significant reduction of 1-cysPrx protein was observed in ASC, PSC, and WC samples, but there was no statistical difference in CS and NS samples relative to normal control. Also, rat lens explants were cultured with 10 ng ml(-1) TGF-beta1 for approximately 5 days or 500 microm H2O2 for approximately 2 days. Subsequently, expression of 1-cysPrx mRNA and protein in the lens capsules was evaluated. Rat lens explants treated with TGF-beta1 or H2O2 developed a cataract similar to human ASC or WC, respectively, which resulted in a markedly decreased expression of 1-cysPrx mRNA and protein. Collectively, these findings show that expression patterns of 1-cysPrx gene in the lens are changed in response to oxidative stress, a major factor in the etiology of cataract.
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PMID:Reduced expression of 1-cys peroxiredoxin in oxidative stress-induced cataracts. 1636 Jun 53

Heat shock protein 27 (Hsp27) is a stress-inducible protein in cells that functions as a molecular chaperone and also as an anti-apoptotic protein. Methylglyoxal (MGO) is a reactive dicarbonyl compound produced from cellular glycolytic intermediates that reacts non-enzymatically with proteins to form products such as argpyrimidine. We found considerable amount of Hsp27 in phosphorylated form (pHsp27) in human cataractous lenses. pHsp27 was the major argpyrimidine-modified protein in brunescent cataractous lenses. Modification by MGO enhanced the chaperone function of both pHsp27 and native Hsp27, but the effect on Hsp27 was at least three-times greater than on pHsp27. Phosphorylation of Hsp27 abolished its chaperone function. Transfer of Hsp27 using a cationic lipid inhibited staurosporine (SP)-induced apoptotic cell death by 53% in a human lens epithelial cell line (HLE B-3). MGO-modified Hsp27 had an even greater effect (62% inhibition). SP-induced reactive oxygen species in HLE-B3 cells was significantly lower in cells transferred with MGO-modified Hsp27 when compared to native Hsp27. In vitro incubation experiments showed that MGO-modified Hsp27 reduced the activity of caspase-9, and MGO-modified pHsp27 reduced activities of both caspase-9 and caspase-3. Based on these results, we propose that Hsp27 becomes a better anti-apoptotic protein after modification by MGO, which may be due to multiple mechanisms that include enhancement of chaperone function, reduction in oxidative stress, and inhibition of activity of caspases. Our results suggest that MGO modification and phosphorylation of Hsp27 may have important consequences for lens transparency and cataract development.
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PMID:Effect of methylglyoxal modification and phosphorylation on the chaperone and anti-apoptotic properties of heat shock protein 27. 1661 38

Oxidative mechanisms are thought to have a major role in cataract formation and diabetic complications. Antioxidant enzymes play an essential role in the antioxidant system of the cells that work to maintain low steady-state concentrations of the reactive oxygen species. When HLE-B3 cells, a human lens cell line were exposed to 50-100 mM glucose for 3 days, decrease of viability, inactivation of antioxidant enzymes, and modulation of cellular redox status were observed. Significant increase of cellular oxidative damage reflected by lipid peroxidation and DNA damage were also found. The glycation-mediated inactivation of antioxidant enzymes may result in the perturbation of cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition and may contribute to various pathologies associated with the long term complications of diabetes.
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PMID:Glycation-induced inactivation of antioxidant enzymes and modulation of cellular redox status in lens cells. 1690 78

Recently, a yellow intraocular lens (IOL) was developed for the purpose of reducing potential blue light-induced retinal damage after cataract surgery. However, the effect of yellow filters on retinal protection remains to be clarified. To test the protective effects of yellow filters on blue light-induced retinal damage, a yellow and a clear soft acrylic filter were attached to the right and left eyes, respectively, of albino rats and exposed to 4.5 k lux blue fluorescent lights with peak wavelength at 420 nm (ranging 380-500 nm; short blue) or 446 nm (ranging 400-540 nm; long blue) for 6h. To assess retinal damage, the electroretinogram (ERG) was recorded at 7 days, outer nuclear layer (ONL) thickness and area were measured at 7 days, apoptosis was analyzed by TUNEL staining at 24 h, and the level of lipid peroxidation in retinas was assessed by Western dot blots using specific antibodies against 4-hydroxynonenal (4-HNE)- and carboxyethylpyrrole (CEP)-modified proteins immediately after light exposure. After short blue light exposure, a- and b-wave ERG amplitudes and the ONL thickness at 1-2.5 mm inferior and 0.5-2.5 mm superior to optic nerve head (ONH) were significantly reduced. TUNEL staining in the ONL at 0-2 mm inferior and 1-2 mm superior to the ONH, and retinal levels of 4-HNE- and CEP-modified proteins were significantly increased in the clear filter-covered eyes compared to yellow filter-covered eyes. After long blue light exposure, the only difference seen was a greater ONL thickness at 1.5 mm superior to the ONH in yellow filter-covered eye. Transmission of light through the yellow filter was 58% for short blue and 89% for long blue compared to the clear filter. The ONL area was not different between clear filter-covered and -uncovered eyes after exposure to short or long blue light. Given the results, yellow IOL material protects the retina against acute shorter wavelength blue light exposure more effectively than the clear IOL material.
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PMID:Protective effects of soft acrylic yellow filter against blue light-induced retinal damage in rats. 1699 96

We previously found that Ca2+ concentrations, inducible nitric oxide synthase (iNOS) mRNA, and protein expression in lenses of the Shumiya cataract rat (SCR) increase with the development of cataracts. In this study, we investigated the change in Ca2+-ATPase activities and ATP levels in the human lens epithelial cell line SRA 01/04 (HLE cells) with the stimulation of interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Expression levels of iNOS mRNA in HLE cells, which were determined using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR methods, increased during stimulation with IFN-gamma (1000 IU) and LPS (100 ng/ml). NO release from HLE cells, expressed as the sum of NO2- and NO3- levels, increased with the increase in iNOS expression levels. Ca2+-ATPase activities increased and ATP levels decreased in HLE cells stimulated with the combination of IFN-gamma and LPS. Furthermore, both diethyldithiocarbamate and aminoguanidine attenuated the increase in Ca2+-ATPase activities and the decrease in ATP levels. These results suggest that excessive production of NO may cause mitochondrial damage, resulting in an increased Ca2+ concentration in the lens. The increase in Ca2+ concentration in the lens may increase Ca2+-ATPase activities.
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PMID:Inhibitors of inducible nitric oxide synthase prevent damage to human lens epithelial cells induced by interferon-gamma and lipopolysaccharide. 1701 54


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