Insulin-like growth factor I in inclusion-body myositis and human muscle cultures

Journal of Neuropathology and Experimental Neurology
Aldobrando BroccoliniMassimiliano Mirabella

Abstract

Possible pathogenic mechanisms of sporadic inclusion-body myositis (sIBM) include abnormal production and accumulation of amyloid beta (A beta), muscle aging, and increased oxidative stress. Insulin-like growth factor I (IGF-I), an endocrine and autocrine/paracrine trophic factor, provides resistance against A beta toxicity and oxidative stress in vitro and promotes cell survival. In this study we analyzed the IGF-I signaling pathway in sIBM muscle and found that 16.2% +/- 2.5% of nonregenerating fibers showed increased expression of IGF-I, phosphatidylinositide 3'OH-kinase, and Akt. In the majority of sIBM abnormal muscle fibers, increased IGF-I mRNA and protein correlated with the presence of A beta cytoplasmic inclusions. To investigate a possible relationship between A beta toxicity and IGF-I upregulation, normal primary muscle cultures were stimulated for 24 hours with the A beta(25-35) peptide corresponding to the biologically active domain of A beta. This induced an increase of IGF-I mRNA and protein in myotubes at 6 hours, followed by a gradual reduction thereafter. The level of phosphorylated Akt showed similar changes. We suggest that in sIBM. IGF-I overexpression represents a reactive response to A beta toxicity, pos...Continue Reading

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Citations

Oct 6, 2007·Current Opinion in Rheumatology·Valerie Askanas, W King Engel
Feb 1, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mario PescatoriEnzo Ricci
Nov 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Roberta MorosettiGiulio Cossu
Sep 13, 2005·Current Opinion in Neurology·Anders Oldfors, Christopher Lindberg
Feb 9, 2012·The American Journal of Pathology·Roberta MorosettiMassimiliano Mirabella
Feb 8, 2005·Neuromuscular Disorders : NMD·Aldobrando BroccoliniMassimiliano Mirabella
Oct 17, 2008·Neurobiology of Aging·Anna NogalskaValerie Askanas

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