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K.–S. Lee, Y. Seomun, C.–K. Joo; Lens epithelial cell cycle arrest by Hydrogen peroxide through the induction of p21 . Invest. Ophthalmol. Vis. Sci. 2004;45(13):403.
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Purpose: Oxidative stress is a candidate for cataractogenesis. Many researchers have been studied the mechanism of cataract, and some factors including various cytokines, UV irradiation, and oxidative stress were suspected to formation of cataract. In this study, we examined the effect of H2O2 in lens epithelial cells (HLE B3). Methods: HLE B3 cells were treated with various concentrations of H2O2. Cell cycle distribution of HLE B3 cells was determined by flow cytometric analysis. After 16hrs of H2O2 treatment, the expression of cell cycle regulators was examined by western blot and Northern blot analysis. Various kinase inhibitors were treated 30minutes or 1hr before H2O2 added. Results: 200µM H2O2 induced G2/M cell cycle arrest and p21 that a regulator of cell cycle was strongly increased. The induction of p21 was partially reduced with treatment of ERK inhibitor (U0126), p38 inhibitor (SB201580) and JNK/SAPK inhibitor (SP600125), respectively. The activation of these kinase was not occurred at the same time point, meaning that two or more signal pathways regulate the induction of p21 by H2O2. Conclusions: H2O2 induce cell cycle arrest in Lens epithelial cells, and ERK p38 and JNK signal pathways differently regulate p21 gene expression. The transcription factor Sp–1 is involved in the regulation of p21 gene. Abnormal cell cycle arrest by H2O2 in lens epithelial cells can explain that oxidative stress may be associate the Cataract formation.
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