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- W2034234265 abstract "purpose. To compare PDGF- and insulin/IGF-1–induced class IA PI 3-kinase/Akt survival signaling in normal retinas and retinal ganglion cells (RGCs). methods. Normal rat retinas and RGC-5 cells were used for (1) immunohistochemical and immunoblot studies to detect PDGF receptor (PDGFR) subtypes and (2) immunoprecipitation, immunoblot, and in vitro lipid kinase assays to determine basal and PDGF-induced class IA PI 3-kinase/Akt survival signaling, in comparison with insulin or IGF-1 responses. Furthermore, RGC-5 cells were exposed to broad-spectrum (LY294002) or p110 isoform-selective (PI-103) PI 3-kinase inhibitors (versus Akt inhibitor) to assess the consequent effects on Akt phosphorylation, caspase-3/PARP cleavage, apoptotic phenotype, and cell viability, as a function of serum trophic factors. results. PDGFR-α and -β immunoreactivity was observed in rat retinal Müller cells and in the RGC layer and blood vessels, respectively. In addition, PDGFR-α and -β protein expression was observed in RGC-5 cells. Both retinas and RGC-5 cells exhibited a similar pattern of subunit-specific basal class IA PI 3-kinase activity, which was stimulated in a temporal and signal-specific manner by PDGF and insulin/IGF-1. Furthermore, RGC-5 cells showed PDGFR-α/β tyrosine phosphorylation that induced the p85α regulatory subunit to activate p110α/β-associated class IA PI 3-kinase, which in turn enhanced Akt phosphorylation. Exposure of serum-deprived RGC-5 cells to PI 3-kinase or Akt inhibitors increased susceptibility to apoptotic phenotype as revealed by caspase-3 and PARP cleavage. conclusions. The present findings provide direct evidence of two distinct modes of retinal class IA PI 3-kinase activation that occurs in response to PDGF receptor and insulin/IGF-1 receptor stimulation. PDGF-induced PI 3-kinase/PIP3/Akt axis may provide new therapeutic approaches to ameliorate cell death in diabetic retinopathy and other retinal neurodegenerations." @default.
- W2034234265 created "2016-06-24" @default.
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- W2034234265 date "2008-08-01" @default.
- W2034234265 modified "2023-09-26" @default.
- W2034234265 title "PDGF- and Insulin/IGF-1–Specific Distinct Modes of Class I<sub>A</sub>PI 3-Kinase Activation in Normal Rat Retinas and RGC-5 Retinal Ganglion Cells" @default.
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- W2034234265 doi "https://doi.org/10.1167/iovs.07-1455" @default.
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- W2034234265 hasPublicationYear "2008" @default.
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