title: Deficiency of insulin-like growth factor-1 receptor confers resistance to oxidative stress in C2C12 myoblasts.
abstract: IGF-1 receptor (IGF-1R) signaling regulates cell growth, transformation and survival. Haploinsufficiency of the IGF-1R is reported to paradoxically confer resistance to oxidative stress in vivo and in cells cultured from Igf1r(+/-) mice. In order to determine whether IGF-1R deficiency directly confers resistance to oxidative stress in specific cell types, an siRNA-mediated approach was applied to reduce IGF-1R in C2C12 myoblasts, NIH3T3 fibroblasts and MC3T3-E1 osteoblasts. Treating the IGF-1R deficient myoblasts with H2O2 resulted in significantly higher phosphorylation of Akt as compared to cells having normal expression of IGF-1R. Similar results were obtained with UV treatment, another inducer of oxidative stress. This enhanced activation of Akt was associated with reduced level of cleaved caspase-3 and PARP. Moreover, in the IGF-1R knockdown myoblasts, phosphorylation of the Akt substrate Bad was enhanced after peroxide treatment. However, in NIH-3T3 fibroblasts and MC3T3-E1 osteoblasts, the loss of IGF-1R by siRNA directed knockdown was associated with reduced levels of phosphorylated Akt on treatment with H2O2 or UV as compared to control cells and these cells showed more apoptosis. These results suggest a novel mechanism of cell type specific differential regulation of resistance to oxidative stress induced apoptosis by reduced levels of IGF-1R.
authors.affiliation: Department of Biochemistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Sachin
authors.initials: S
authors.lastname: Thakur
authors.forename: Neha
authors.initials: N
authors.lastname: Garg
authors.forename: Martin L
authors.initials: ML
authors.lastname: Adamo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000172:deficiency* / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D051025:bcl-Associated Death Protein; D006861:Hydrogen Peroxide; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt