Inhibition of PI3K/Akt pathway impairs G2/M transition of cell cycle in late developing progenitors of the avian embryo retina

• Published in: PloS one Vol. 8; no. 1; p. e53517
• Main Authors: Ornelas, Isis Moraes, Silva, Thayane Martins, Fragel-Madeira, Lucianne, Ventura, Ana Lucia Marques
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.01.2013; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Biology; Cell Cycle; Cell death; Cell Division; Cell growth; Cell Proliferation; Cell survival; Cells, Cultured; Cellular signal transduction; Central nervous system; Chick Embryo; Chromones - pharmacology; Cyclin B1; Cyclin B1 - metabolism; Cyclin-dependent kinases; Explants; G2 Phase; Gene Expression Regulation, Developmental; Histone H3; Histones - metabolism; Immunofluorescence; Kinases; Laboratory animals; Localization; Microscopy, Fluorescence; Mitosis; Morpholines - pharmacology; Neurobiology; Neurosciences; Phase transitions; Phosphatase; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Retina; Retina - cytology; Retina - embryology; Retina - metabolism; Retinal cells; Signal Transduction; Stem Cells - cytology; Time Factors; Tissues; Ventricle; Brazil; Rio de Janeiro Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053517

PI3K/Akt is an important pathway implicated in the proliferation and survival of cells in the CNS. Here we investigated the participation of the PI3K/Akt signal pathway in cell cycle of developing retinal progenitors. Immunofluorescence assays performed in cultures of chick embryo retinal cells and intact tissues revealed the presence of phosphorylated Akt and 4E-BP1 in cells with typical mitotic profiles. Blockade of PI3K activity with the chemical inhibitor LY 294002 (LY) in retinal explants blocked the progression of proliferating cells through G2/M transition, indicated by an expressive increase in the number of cells labeled for phosphorylated histone H3 in the ventricular margin of the retina. No significant level of cell death could be detected at this region. Retinal explants treated with LY for 24 h also showed a significant decrease in the expression of phospho-Akt, phospho-GSK-3 and the hyperphosphorylated form of 4E-BP1. Although no change in the expression of cyclin B1 was detected, a significant decrease in CDK1 expression was noticed after 24 h of LY treatment both in retinal explants and monolayer cultures. Our results suggest that PI3K/Akt is an active pathway during proliferation of retinal progenitors and its activity appears to be required for proper CDK1 expression levels and mitosis progression of these cells.