title: Age-associated increase in cleaved caspase 3 despite phosphorylation of IGF-1 receptor in the rat retina.
abstract: Diseases of aging produce many alterations in the retina, but changes in growth factor signaling in normal aging are less characterized. This study investigated modifications in insulin-like growth factor-1 (IGF-1) receptor (IGF-1R) signaling in the retina of Brown Norway x Fischer 344 F1 hybrid rats at 8, 22, and 32 months. Immunoblotting for proteins involved in IGF-1R signal transduction and electroretinograms were done to evaluate changes with aging. Aging produced a significant decrease in b-wave and oscillatory potential amplitudes in the retina. Aging produced increased phosphorylation of IGF-1R. Despite the increase in IGF-1R activity, insulin receptor substrate-1 (IRS-1) phosphorylation was significantly decreased with increasing age. Akt activity was significantly decreased at 22 and 32 months of age, resulting in increased cleaved caspase 3 levels. The results suggest that regulation of IRS-1 phosphorylation may modulate apoptotic rates in the aging retina, potentially preventing activation of vascular endothelial cell growth factor.
authors.affiliation: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Youde
authors.initials: Y
authors.lastname: Jiang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Walker
authors.forename: Jena J
authors.initials: JJ
authors.lastname: Steinle
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D004596:Electroretinography; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D017526:Receptor, IGF Type 1; D053148:Caspase 3
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