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Eur J Neurosci ; 22(1): 28-38, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16029193

ABSTRACT

Transforming growth factor (TGF)-beta and insulin display opposite effects in regulating programmed cell death during vertebrate retina development; the former induces apoptosis while the latter prevents it. In the present study we investigated coordinated actions of TGF-beta and insulin in an organotypic culture system of early postnatal mouse retina. Addition of exogenous TGF-beta resulted in a significant increase in cell death whereas exogenous insulin attenuated apoptosis and was capable of blocking TGF-beta-induced apoptosis. This effect appeared to be modulated via insulin-induced transcriptional down-regulation of TGF-beta receptor II levels. The analysis of downstream signalling molecules also revealed opposite effects of both factors; insulin provided survival signalling by increasing the level of anti-apoptotic Bcl-2 protein expression and phosphorylation and down-regulating caspase 3 activity whereas pro-apoptotic TGF-beta signalling reduced Bcl-2 mRNA levels and Bcl-2 phosphorylation and induced the expression of TGF-induced immediate-early gene (TIEG), a Krüppel-like zinc-finger transcription factor, mimicking TGF-beta activity.


Subject(s)
Apoptosis/physiology , Insulin/metabolism , Neurons/metabolism , Retina/growth & development , Retina/metabolism , Transforming Growth Factor beta/metabolism , Animals , Animals, Newborn , Apoptosis/drug effects , Caspase 3 , Caspases/genetics , Caspases/metabolism , Cell Differentiation/drug effects , Cell Differentiation/physiology , Cells, Cultured , DNA-Binding Proteins/drug effects , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Down-Regulation/drug effects , Down-Regulation/physiology , Drug Interactions/physiology , Gene Expression Regulation, Developmental/drug effects , Gene Expression Regulation, Developmental/genetics , Insulin/pharmacology , Mice , Mice, Inbred C57BL , Neurons/drug effects , Organ Culture Techniques , Organogenesis/drug effects , Organogenesis/physiology , Phosphorylation/drug effects , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Receptor, Transforming Growth Factor-beta Type II , Receptors, Transforming Growth Factor beta/drug effects , Receptors, Transforming Growth Factor beta/genetics , Receptors, Transforming Growth Factor beta/metabolism , Retina/drug effects , Smad Proteins , Trans-Activators/drug effects , Trans-Activators/genetics , Trans-Activators/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Transcriptional Activation/drug effects , Transcriptional Activation/genetics , Transforming Growth Factor beta/pharmacology , Up-Regulation/drug effects , Up-Regulation/physiology
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