title: Involvement of IGF-II receptors in the antioxidant and neuroprotective effects of IGF-II on adult cortical neuronal cultures.
abstract: Insulin-like growth factor-II (IGF-II) is a naturally occurring peptide that exerts known pleiotropic effects ranging from metabolic modulation to cellular development, growth and survival. IGF-II triggers its actions by binding to and activating IGF (IGF-I and IGF-II) receptors. In this study, we assessed the neuroprotective effect of IGF-II on corticosterone-induced oxidative damage in adult cortical neuronal cultures and the role of IGF-II receptors in this effect. We provide evidence that treatment with IGF-II alleviates the glucocorticoid-induced toxicity to neuronal cultures, and this neuroprotective effect occurred due to a decrease in reactive oxygen species (ROS) production and a return of the antioxidant status to normal levels. IGF-II acts via not only the regulation of synthesis and/or activity of antioxidant enzymes, especially manganese superoxide dismutase, but also the restoration of mitochondrial cytochrome c oxidase activity and mitochondrial membrane potential. Although the antioxidant effect of IGF-I receptor activation has been widely reported, the involvement of the IGF-II receptor in these processes has not been clearly defined. The present report is the first evidence describing the involvement of IGF-II receptors in redox homeostasis. IGF-II may therefore contribute to the mechanisms of neuroprotection by acting as an antioxidant, reducing the neurodegeneration induced by oxidative insults. These results open the field to new pharmacological approaches to the treatment of diseases involving imbalanced redox homeostasis. In this study, we demonstrated that the antioxidant effect of IGF-II is at least partially mediated by IGF-II receptors.
authors.affiliation: Department of Pharmacology and Paediatrics, Malaga University, Biomedical Research Institute of Malaga (IBIMA), E-29071 Malaga, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Martin-Montañez
authors.affiliation: Department of Pharmacology and Paediatrics, Malaga University, Biomedical Research Institute of Malaga (IBIMA), E-29071 Malaga, Spain; Clinical Neurosciences Unit, Research Laboratory and Microscopy Unit, Biomedical Research Institute of Malaga (IBIMA), Regional University Hospital of Malaga, E-29010 Málaga, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Pavia
authors.affiliation: Department of Psychobiology, Malaga University, Biomedical Research Institute of Malaga (IBIMA), E-29071 Malaga, Spain.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Santin
authors.affiliation: Department of Life Sciences, University of Modena e Reggio Emilia, I-41010 Modena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Boraldi
authors.affiliation: Clinical Neurosciences Unit, Research Laboratory and Microscopy Unit, Biomedical Research Institute of Malaga (IBIMA), Regional University Hospital of Malaga, E-29010 Málaga, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Estivill-Torrus
authors.affiliation: Department of Human Physiology, Malaga University, Biomedical Research Institute of Malaga (IBIMA), E-29071 Malaga, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Aguirre
authors.affiliation: Department of Human Physiology, Malaga University, Biomedical Research Institute of Malaga (IBIMA), E-29071 Malaga, Spain. Electronic address: igf@uma.es.
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia-Fernandez
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D003576:Electron Transport Complex IV / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism* / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005938:Glucocorticoids; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV
keywords: Antioxidant; Insulin like growth factor-II; Insulin like growth factor-II receptor; Mitochondria; Neurodegeneration; Neuroprotective