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- Celojevic, Dragana, 1985, et al.
(författare)
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Effects of 17beta-estradiol in human lens epithelial cells
- 2010
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Ingår i: Acta Ophthalmologica. 2010;88:S246. Presented at European Vision and Eye Research (EVER) Annual Meeting 2010, 6-9 Oct, Crete, Greece.. - : Wiley.
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Konferensbidrag (refereegranskat)
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| 2. |
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| 3. |
- Celojevic, Dragana, 1985, et al.
(författare)
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Superoxide dismutase gene polymorphisms in patients with age-related cataract
- 2013
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Ingår i: Ophthalmic genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; 34:3, s. 140-145
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Functional polymorphisms in genes encoding antioxidant enzymes may result in reduced enzyme activity and increased levels of reactive oxygen species, such as superoxide radicals, which in turn may contribute to increased risk of age-related disorders. Copper-zinc superoxide dismutases, SOD-1 and SOD-3, and manganese superoxide dismutase, SOD-2, are enzymes involved in the protection against oxidative stress and detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) of SOD1, SOD2 and SOD3, in patients with age-related cataract. MATERIALS AND METHODS: The study included an Estonian sample of 492 patients with age-related cataract, subgrouped into nuclear, cortical, posterior subcapsular and mixed cataract, and 185 controls. Twelve SNPs in SOD1, SOD2 and SOD3 were genotyped using TaqMan Allelic Discrimination. Haplotype analysis was performed on the SNPs in SOD2. RESULTS: None of the studied SNPs showed an association with risk of cataract. These results were consistent after adding known risk factors (age, sex and smoking) as covariates in the multivariate analyses and after stratification by cataract subtype. Analysis of SOD2 haplotypes did not show any associations with risk of cataract. CONCLUSIONS: If genetic variation in genes encoding SOD-1, SOD-2 and SOD-3 contributes to cataract formation, there is no major contribution of the SNPs analyzed in the present study.
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| 4. |
- Jonhede, Sofia, et al.
(författare)
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Acute effects of the sigma-2 receptor agonist siramesine on lysosomal and extra-lysosomal proteolytic systems in lens epithelial cells
- 2010
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Ingår i: Molecular Vision. - 1090-0535. ; 16, s. 819-827
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of the present study was to examine the effects of the sigma-2 receptor agonist, siramesine, on morphology, growth, cell death, lysosomal function, and effects on extra-lysosomal proteolytic systems in human lens epithelial cells. Methods: Human lens epithelial cells in culture were exposed to siramesine and examined for morphological changes using Nomarski optics or calcein. Lysosomes were evaluated using acridine orange and Magic Red (RR-cresyl violet). Nuclear morphology was studied using Hoechst 33342 and propidium iodide. Enzymatic activities in living cells or cell lysates were studied using fluorogenic substrates. Results: Siramesine at low concentrations increased the cytoplasmic proteolytic activity of the proteasome and the calpain system. Effects were also observed with respect to lysosomal morphology, acidity and function. In addition, activation of caspase-3 and the appearance of nuclei with an apoptotic morphology was found. Conclusions: Siramesine at low concentrations affects lens epithelial cells with perturbations of the major proteolytic systems and lysosomal morphology, resulting in caspase activation and cell death. Siramesine may be a possible substance for the treatment or prevention of posterior capsular opacification (PCO).
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| 5. |
- Karlsson, Jan-Olof, 1944, et al.
(författare)
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Acute Effects of Indomethacin on Mitochondrial Function and Glutathione Levels in the Mouse Lens in Organ Culture
- 2003
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Ingår i: Invest. Ophthalmol. Vis. Sci.. ; 44:5, s. 3500-
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Konferensbidrag (refereegranskat)abstract
- Purpose, Experiments were carried out to study the effects of indomethacin on markers for oxidative damage and mitochondrial function in the intact mouse lens. Methods, Mouse lenses were incubated with fluorogenic indicator dyes prior to administration of 50 {micro}M indomethacin. The response was monitored, in real time, for several hours. Mitochondrial depolarization was followed by preloading the lens with Rhodamine 123 (10 {micro}g/ml). Peroxide production was studied in lenses loaded with 50{micro}M DCF-DA and superoxide levels with 10 {micro}M hydroethidium. Glutathione levels were assayed with 50 {micro}M monochlorobimane following short-term administration of indomethacin. Results, No significant changes in the production of peroxide or superoxide were found up to 3 hours after administration of indomethacin. The level of reduced glutathione was reduced by approximately 10 percent 3 h after drug administration. There was a significant increase (20%) of mitochondrial depolarization, compared to control lenses, one hour following indomethacin administration. Conclusions, The frequent use of nonsteroidal anti-inflammatory drugs in ophthalmology necessitates a close examination of effects besides the anti-inflammatory ones. This study points to relatively rapid effects on mitochondrial function and glutathione levels in the cultured mouse lens. The possible relation between these changes and the development of cataract remains to be studied.
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| 6. |
- Karlsson, Jan-Olof, 1944, et al.
(författare)
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Acute Effects of the Sigma-2 Receptor Agonist Siramesine on Lens Epithelial Cells
- 2007
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Ingår i: Invest. Ophthalmol. Vis. Sci.. ; 48:5, s. 2432-
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Konferensbidrag (refereegranskat)abstract
- PurposeExperiments were carried out to study the effects of siramesine on markers for apoptosis, oxidative damage and mitochondrial function in primary cultures of human lens epithelial cells (HLEC). MethodsHLEC were incubated with 25 {micro}M siramesine for 1, 2, 3, 4, 6 and 8 hours. Caspase-3 was assayed in cell extracts with DEVD-AMC. Mitochondrial depolarization was assayed with JC-1. Peroxide production was studied with DCF-DA and superoxide levels with hydroethidium. Glutathione levels were assayed with monochlorobimane. ResultsSiramesine induced a significant increase of caspase-3 activity after 6h exposure to 25 {micro}M siramesine. Nuclear morphology examined with Hoechst 33342 showed signs of apoptosis after the same time intervals. A significant increase in the production of peroxide and superoxide were found up to 4 -8 hours after administration of siramesine. ConclusionsSiramesine, a piperidine analogue, was developed for the treatment of psychiatic disorders and is considered to be relatively nontoxic. This study, and others, indicate effects on cell growth, apoptosis and production of ROS. The sigma-2 receptor may be a regulator of HLEC growth and apoptosis.
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| 9. |
- Karlsson, Jan-Olof, 1944, et al.
(författare)
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Inhibition Of Glycogen Synthase Kinase (gsk-3) Affects Markers Of Oxidative Stress And Attenuates Apoptosis In Human Lens Epithelial Cells
- 2004
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Ingår i: Invest. Ophthalmol. Vis. Sci.. ; 45:5, s. 3508-
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Konferensbidrag (refereegranskat)abstract
- Purpose: GSK-3, an evolutionary conserved S/T kinase which regulates cell fate determination in diverse organisms have been implicated in the formation of amyloid b-peptides and the phosphorylation of tau and catenin. Inhibition of GSK-3 can be obtained via the structurally unrelated substances lithum or Kenpaullone. The lens and the lens epithelial cells are excellent models to study the role of this enzyme. Methods: Confluent human lens epithelial cells (HLEC) were exposed to the GSK-3 inhibitors lithium (2 mM) or Kenpaullone (2 {micro}M) for times upp to 24h. The cells were, before or after treatment, placed in medium containing fluorogenic indicators of oxidative damage. DCFH-DA was used to assay peroxides, mitochondrial function was evaluated with Rhodamine 123, monochlorobimane was used to assay intracellular glutathione (GSH) levels, Proteolytic activities were assayed, on line, with cell-permeable fluorogenic substrates.Proteasome and calpain activities were assayed with LLVY-AMC, Cathepsin B with RR-AMC or FR-AMC. Metalloproteases were assayed with AAF-AMC. Caspase-3, 8 and 9 were assayed in cell extracts with DEVD-, IETD- or LEHD-AMC, respectively. Results: The mitochondrial membrane potential and the level of GSH increased by 10% after treatment with Li or Kenpaullone for 24h. No change was observed for peroxide production. The basal (low) level of caspase-3 activity was decreased by 20%. No significant effects were found concerning caspase-8 or 9 activities. No effect was observed on the activity of calpain, the proteasome, metalloproteases and cathepsin D/E activity. Conclusions:Inhibition of GSK-3 may protect against oxidative damage and attenuate apoptosis in HLEC. No changes of the other major proteolytic systems in the cell were detected. These data may be important for the interpretation of Wnt signaling and cell growth in HLEC as well as for the formation of amyloid in the lens.
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| 10. |
- Karlsson, Jan-Olof, 1944, et al.
(författare)
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Inhibition of Glycogen Synthase Kinase (GSK-3) Protects Against Oxidative Stress and Attenuates Apoptosis in Human Lens Epithelial Cells and the Mouse Lens in Organ Culure
- 2005
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Ingår i: Invest. Ophthalmol. Vis. Sci.. ; 46:5, s. 3867-
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Konferensbidrag (refereegranskat)abstract
- Purpose: GSK-3 may regulate Wnt signaling, gene expression, the cell cycle, cell differentiation and apoptosis. Inhibition of GSK-3 can be obtained via the structurally unrelated substances lithum or Kenpaullone. The lens and the lens epithelial cells are excellent models to study the role of this enzyme. Methods: Primary cultures of human lens epithelial cells (HLEC) or the mouse lens in organ culture were exposed to the GSK-3 inhibitors lithium (2 mM) or Kenpaullone (2 {micro}M) for times upp to 24h.The cells were, before or after treatment, placed in medium containing fluorogenic indicators of oxidative damage. DCFH-DA was used to assay peroxides, mitochondrial function was evaluated with Rhodamine 123 and JC-1, monochlorobimane was used to assay intracellular glutathione (GSH) levels, Proteolytic activities were assayed, on line, with cell-permeable fluorogenic substrates.Proteasome and calpain activities were assayed with LLVY-AMC, Cathepsin B with RR-AMC or FR-AMC. Metalloproteases were assayed with AAF-AMC. Caspase-3, 8 and 9 were assayed in cell extracts with DEVD-, IETD- or LEHD-AMC, respectively. Results: The mitochondrial membrane potential and the level of GSH increased by 10% after treatment of HLEC with Li or Kenpaullone for 24h. No change was observed for peroxide production. The basal (low) level of caspase-3 activity was decreased by at least 20%. No significant effects were found concerning caspase-8 or 9 activities. No effect was observed on the activity of calpain, the proteasome, metalloproteases and cathepsin D/E activity.The whole mouse lens in organ culture showed essentially the same elevated mitochondrial potential. The GSH increase was even more evident in the whole lens preparation. Conclusions: Inhibition of GSK-3 may protect against oxidative stress (and cataract) via prevention of MPT induction and attenuate apoptosis in HLEC.
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