Phosphorylation/inactivation of PTEN by Akt-independent PI3K signaling in retinal pigment epithelium

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Retinal pigment epithelium (RPE) plays a critical role in vertebrate vision by providing functional and structural support to the retina. Degeneration of RPE by cumulative oxidative stresses or acute injury frequently results in retinal degenerative diseases, notably age-related macular degeneration (AMD). Moreover, it has been shown that phosphorylation-mediated inactivation of PTEN (phosphatase and tensin homolog) in RPE is closely linked to AMD-like retinal degeneration in mice Ill. In this study, we used AMD mouse models, in which chemokine (C-C motif) ligand 2 (Ccl2) or chemokine (C-C motif) receptor 2 (Ccr2) were genetically ablated, to examine mechanisms linking reactive oxygen species (ROS) to phosphorylation/inactivation of PTEN in RPE. We found that ROS levels were increased in these RPE cells in association with phosphorylation/inactivation of PTEN. Both PTEN phosphorylation/inactivation and consequent Akt activation in the RPE of AMD model mice were inhibited by antioxidant treatment, indicating a functional role for elevated intracellular ROS. We further discovered that PTEN phosphorylation in oxidatively stressed RPE was repressed by a phosphoinositide 3-kinase (PI3K) inhibitor, but not by an Akt inhibitor. Taken together, these results suggest that ROS-activated PI3K potentiates AMD-related RPE pathogenesis through phosphorylation/inactivation of PTEN. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Issue Date
2011-10
Language
English
Article Type
Article
Keywords

MACULAR DEGENERATION; SODIUM IODATE; MICE; PATHWAY; MODEL; DYSFUNCTION; ACTIVATION; MECHANISMS; LIPOFUSCIN; APOPTOSIS

Citation

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.414, no.2, pp.384 - 389

ISSN
0006-291X
URI
http://hdl.handle.net/10203/97234
Appears in Collection
BS-Journal Papers(저널논문)
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