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Insulin‐like growth factor‐I is a potential trophic factor for amacrine cells
Author(s) -
Politi Luis E.,
Rotstein Nora P.,
Salvador Gabriela,
Giusto Norma M.,
Insua M. Fernanda
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00128.x
Subject(s) - wortmannin , neurite , insulin like growth factor , biology , growth factor , microbiology and biotechnology , endocrinology , medicine , insulin , protein kinase b , signal transduction , receptor , biochemistry , in vitro
In this study we show that insulin‐like growth factor (IGF)‐I selectively promotes survival and differentiation of amacrine neurons. In cultures lacking this factor, an initial degeneration pathway, selectively affecting amacrine neurons, led to no lamellipodia development and little axon outgrowth. Cell lysis initially affected 50% of amacrine neurons; those remaining underwent apoptosis leading to the death of approximately 95% of them by day 10. Apoptosis was preceded by a marked increase in c‐Jun expression. Addition of IGF‐I or high concentrations (over 1 µ m ) of either insulin or IGF‐II to the cultures prevented the degeneration of amacrine neurons, stimulated their neurite outgrowth, increased phospho‐Akt expression and decreased c‐Jun expression. The high insulin and IGF‐II concentrations required to protect amacrine cells suggest that these neurons depend on IGF‐I for their survival, IGF‐II and insulin probably acting through IGF‐I receptors to mimic IGF‐I effects. Inhibition of phosphatidylinositol‐3 kinase (PI 3‐kinase) with wortmannin blocked insulin‐mediated survival. Wortmannin addition had similar effects to IGF‐I deprivation: it prevented neurite outgrowth, increased c‐Jun expression and induced apoptosis. These results suggest that IGF‐I is essential for the survival and differentiation of amacrine neurons, and activation of PI 3‐kinase is involved in the intracellular signaling pathways mediating these effects.