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• W2045403409 endingPage "4614" @default.
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• W2045403409 abstract "Oxidative stress is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which involves retinal pigmented epithelial (RPE) cell death. However, signaling pathways involved in the oxidative-stress-induced RPE cell death are poorly understood. This study was conducted to investigate the involvement of the MAP kinase pathways during the induction of RPE cell death by oxidative stress.ARPE-19 cells were exposed to the oxidant tert-butyl hydroperoxide (t-BHP). Cell viability was assessed by cell counting and MTT-staining, and apoptosis was quantified by TUNEL and flow cytometry. Activation of JNK1/3, p38 alphabeta MAPKs and ERK1/2 and their potential targets was detected by Western blot analysis and immunochemistry with specific anti-phospho protein antibodies. Specific pharmacologic inhibitors directed against the MAPKs were used to analyze the signaling involved in cell death of RPE cells exposed to t-BHP.Exposure of RPE cells to t-BHP, associated with increase in reactive oxygen species and intracellular glutathione depletion, induced time- and concentration-dependent apoptosis, which was associated with the accumulation of inactive ERK1/2 in cell nuclei and a transient and weak ERK1/2 activation. This activation was accompanied by a deactivation of P90(RSK), the major target of ERK1/2 and consequently by the delayed activation of its transcription factor CREB. MEK1/2 inhibition completely suppressed the transient activation of ERK1/2 and completely blocked apoptosis, demonstrating the role of the MEK-ERK module in mediating oxidative-stress-induced RPE cell death. In contrast, neither JNKs nor p38 alphabeta MAPKs were involved in mediating t-BHP-induced apoptotic signaling in RPE cells.The results suggest that inhibiting the MEK-ERK module may allow the development of selective methods for treating oxidative-stress-induced RPE degeneration, such as AMD." @default.
• W2045403409 created "2016-06-24" @default.
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• W2045403409 date "2006-10-01" @default.
• W2045403409 modified "2023-10-16" @default.
• W2045403409 title "Sustained versus Transient ERK1/2 Signaling Underlies the Anti- and Proapoptotic Effects of Oxidative Stress in Human RPE Cells" @default.
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• W2045403409 doi "https://doi.org/10.1167/iovs.06-0297" @default.
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