| 1. |
|
|
| 2. |
- Karlsson, Jan-Olof, 1944, et al.
(författare)
-
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
-
Ingår i: Invest. Ophthalmol. Vis. Sci.. ; 46:5, s. 3867-
-
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.
|
|
| 3. |
- Petersen, Anne, 1962, et al.
(författare)
-
The Mechanism of Antioxidant Actions by NSAIDs/ASA in Cultured Human Lens Epithelial Cells
- 2005
-
Ingår i: Invest. Ophthalmol. Vis. Sci.. ; 46:5, s. 3854-
-
Konferensbidrag (refereegranskat)abstract
- Purpose: To study the possible mechanisms for protection against oxidative stress by indomethacin, diclofenac, celecoxib (NSAIDs) or acetylsalicylic acid (ASA) in cultured human lens epithelial cells (HLEC). Methods: Changes in peroxide levels in HLEC was measured after exposure to low concentrations (0, 0.005, 0.05 or 0,5 {micro}M) of indomethacin, diclofenac, celecoxib or acetylsalicylic acid for 24 hours. The cells were assayed at regular intervals during 24 h using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Cultured HLEC were incubated with H2O2 (200 {micro}M) alone or in the presence of NSAIDs/ASA. The cells were then assayed for changes in GSH levels using monochlorobimane (MCB). Results: NSAIDs/ASA at concentrations previous described to be effective against oxidative stress in HLEC did not affect peroxide levels in cultured HLEC. The reducing capacity as measured as the GSH levels, were not significantly changed in oxidatively stressed HLEC. No toxic effects on GSH or peroxide levels were present. Conclusions: Indomethacin, diclofenac, celecoxib or acetylsalicylic acid does not exert their protective actions against oxidative stress via changed levels of endogenous peroxide or GSH.
|
|
| 4. |
- Zetterberg, Henrik, 1973, et al.
(författare)
-
Evolution, exaptation, and stereopsis.
- 2005
-
Ingår i: Archives of ophthalmology. - : American Medical Association (AMA). - 0003-9950. ; 123:9
-
Tidskriftsartikel (refereegranskat)
|
|
| 5. |
|
|
| 6. |
- Zetterberg, Henrik, 1973, et al.
(författare)
-
The szilard hypothesis on the nature of aging revisited.
- 2009
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 182:1, s. 3-9
-
Tidskriftsartikel (refereegranskat)abstract
- This year marks the 50th anniversary of a nearly forgotten hypothesis on aging by Leo Szilard, best known for his pioneering work in nuclear physics, his participation in the Manhattan Project during World War II, his opposition to the nuclear arms race in the postwar era, and his pioneering ideas in biology. Given a specific set of assumptions, Szilard hypothesized that the major reason for the phenomenon of aging was aging hits, e.g., by ionizing radiation, to the gene-bearing chromosomes and presented a mathematical target-hit model enabling the calculation of the average and maximum life span of a species, as well as the influence of increased exposure to DNA-damaging factors on life expectancy. While many new findings have cast doubt on the specific features of the model, this was the first serious effort to posit accumulated genetic damage as a cause of senescence. Here, we review Szilard's assumptions in the light of current knowledge on aging and reassess his mathematical model in an attempt to reach a conclusion on the relevance of Szilard's aging hypothesis today.
|
|
| 7. |
|
|
| 8. |
- Zetterberg, Madeleine, 1969, et al.
(författare)
-
Association of complement factor HY402H gene polymorphism with Alzheimer's disease
- 2008
-
Ingår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-4841. ; 147B:6, s. 720-6
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several epidemiological and biochemical features. The present study aimed to assess the possible influence of the AMD-associated complement factor H (CFH) Y402H (1277T > C) polymorphism on the risk of AD. Caucasian subjects (n=800) meeting the criteria for probable (n = 717) or definite (n = 83) AD and Caucasian non-demented controls (n 1265) were included in this multi-center case-control study, in which genotype and allele frequencies of the CFH 1277T > C polymorphism were determined and related to diagnosis, APOE genotype, Mini-Mental State Examination score (MMSE) and the cerebrospinal fluid (CSF) biomarkers total-tau (T-tau), phospho-tau(181), (P-tau(181)), and beta-amyloid(1-42) (A beta(1-42)). The AMD-associated CFH genotypes (1277CC and 1277TC) were overrepresented in subjects with AD as compared to control individuals (P = 0.029). Positive C carrier status was associated with an odds ratio (OR) for AD of 1.24 (95% confidence interval [CI] 1.02-1.50). When APOE 4 carrier status was included in the regression model, this association was even stronger (OR 1.34, 95% CI: 1.08-1.65, P=0.007). Subgroup analysis showed that the association between CFH C allele positivity and AD was only evident for individuals carrying the APOE epsilon 4 allele. Positive C carrier status was also associated with lower levels of CSF A beta(1-42) selectively in the control group in an APOE epsilon 4-independent manner (P=0.003). In conclusion, the CFH 1277T > C polymorphism seems to influence the risk of AD and there appears to be an interaction between CFH 1277C and APOE epsilon 4 alleles. The CFH 1277C allele may predispose patients for co-morbidity in AD and AMD. (c) 2007 Wiley-Liss, Inc.
|
|
| 9. |
- Zetterberg, Madeleine, 1969, et al.
(författare)
-
Methylenetetrahydrofolate reductase genetic polymorphisms in patients with cataract.
- 2005
-
Ingår i: American journal of ophthalmology. - : Elsevier BV. - 0002-9394. ; 140:5, s. 932-4
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Hyperhomocysteinemia is commonly associated with polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. The level of homocysteine can be lowered by dietary intake of folate. A protective effect of folate supplementation has been reported against cataract. Here we investigate MTHFR polymorphisms in human cataract. DESIGN: Retrospective case-control association study. METHODS: Patients with nuclear (n = 77), cortical (n = 155), posterior subcapsular (n = 119), and mixed (n = 151) cataract, and 187 controls were analyzed for the MTHFR 677C-->T and 1298A-->C polymorphisms using minisequencing technique. RESULTS: The wild-type MTHFR 677CC/1298AA genotype was strongly overrepresented among cataract cases (P = .003). This effect was most pronounced in the mixed cataract group (P < .001). Hyperhomocysteinemia-associated genotypes had similar frequencies in cataract and control groups. CONCLUSIONS: The previously reported protective effect of folate against cataract is not due to overrepresentation of hyperhomocysteinemia-associated MTHFR genotypes. Instead, the strong predominance of wild-type MTHFR in cataract may suggest impaired DNA synthesis as a cataractogenic factor.
|
|
| 10. |
|
|
