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Tianyu Zheng, Yi Lu; Upregulation of Sirt1 Protects Lens Epithelial Cells in Oxidative Conditions and Cataract Formation in Humans. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5291.
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Sirt1, the most well-known sirtuin family (class III histonedeacetylases) member, is involved in many age-related diseases.This study was to investigate its relationship with age-relatedcataract (ARC) and lens epithelial cells (LECs).
The anterior lens capsule from 360 donor eyes was divided into3 groups: young, old and ARC lens. RT-PCR of Sirt1, westernblot of Sirt1 and its downstream proteins, p53, acetyl-p53,FoxO3a, FoxO4, p27kip1, p130 and Bim, immunofluorescence ofSirt1, and TUNEL assay was performed. Human LECs were culturedin H2O2 conditions. Resveratrol, promoter of Sirt1 and Nicotinamide,inhibitor of Sirt1 was applied respectively with different concentration.24h later, MTT analysis, western blot of Sirt1 and its downstreamproteins, immunofluorescence of Sirt1, and TUNEL assay was performed.
Sirt1 expression was significantly decreased in old lens comparedwith young lens, but increased in ARC. Accordingly, the activeacetyl-p53 in ARC lens was decreased and the activity of FoxOproteins was increased, compared with normal old lens (Figure1). In cultured LECs, Sirt1 expression was upregulated in oxidativeconditions, which was further increased by Resveratrol and inhibitedby Nicotinamide. Resveratrol with a concentration of 20µmol/Llargely reduced cell death caused by oxidation. Nicotinamidefurther promoted the oxidative damage and led to fibrosis ofLECs (Figure 2).
The expression of Sirt1 increased in ARC with downstream p53inhibited and FoxO pathway activated. Resveratrol could reduceoxidative damage of LECs via upregulation of Sirt1, suggestingprotections by Sirt1 in oxidative conditions and cataract formation.
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