A stress survival response in retinal cells mediated through inhibition of the serine/threonine phosphatase PP2A

The European Journal of Neuroscience
Sorcha FinneganThomas G Cotter

Abstract

Cell survival signalling involving the PI3K/Akt survival pathway can be negatively regulated by several phosphatases including PP2A. When retinal-derived 661W cells were subjected to trophic factor deprivation this initiated a survival response through inhibition of the activity of PP2A and subsequent upregulation of the Erk and Akt survival pathways. We show this survival response via inhibition of PP2A activity was due in part to increased reactive oxygen species production when retinal cells were deprived of trophic factors. Inhibition of PP2A activity was mediated by a rapid and transient increase in phosphorylation at Tyr307, accompanied by an increase in demethylation and a decrease in the methylated form. Pre-treatment with N-acetyl-L-cysteine, which is involved in scavenging reactive oxygen species, prevented PP2A inhibition and subsequent upregulation of survival pathways. Pre-treatment with the Src family kinase inhibitor PP2 resulted in approximately 50% reduction in cellular levels of phospho-PP2A in trophic factor-deprived 661W cells, suggesting an Src tyrosine kinase had a role to play in this redox regulation of cell survival. We observed similar events in the rd10 mouse retina where there was an increased surviv...Continue Reading

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Citations

Oct 24, 2012·Journal of Bioenergetics and Biomembranes·Nathan R PerronBärbel Rohrer
Apr 22, 2011·Critical Reviews in Oncology/hematology·José L SardinaAngel Hernández-Hernández
Apr 18, 2018·Molecular Neurodegeneration·Alonso Sánchez-CruzCatalina Hernández-Sánchez

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