Insulin-like growth factor I (IGF-I) receptors and IGF-I action in oligodendrocytes from rat brains

Brian A. Masters, Haim Werner, Charles T. Roberts, Derek LeRoith, Mohan K. Raizada

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    34 Scopus citations

    Abstract

    Oligodendrocyte progenitor cells were prepared by mechanical dissociation of 1-day-old rat brain cultures. These cells undergo proliferation and differentiation into oligodendrocytes as demonstrated by the expression of proliferation and differentiation-related specific antigens. We have used this unique culture system to characterize insulin-like growth factor I (IGF-I) receptors and their action in the central nervous system (CNS). 125I-IGF-I specifically binds to these cultures with high affinity. Competition-inhibition data suggest that IGF-I is most potent in competing for 125I-IGF-I binding, followed by IGF-II and insulin. Scatchard analyses of the binding data indicate a curvilinear plot with a Kd for high affinity of 0.2 nM, and a Bmax of 247 fmol/mg, and a Kd for low affinity of 3.2 nM and Bmax of 1213 fmol/mg protein. Covalent cross-linking followed by SDS-PAGE analysis demonstrated a radioactive band of Mr 135,000 which corresponds to the α subunit of the IGF-I receptor. Solution hybridization/RNase protection assay produced a single protected band corresponding to IGF-I receptor messenger RNA, further confirming the presence of these receptors. Incubation of progenitor cells with IGF-I resulted in a time- and concentration-dependent increase in [3H]thymidine incorporation and cell numbers. This effect appears to be mediated by IGF-I receptors since IGF-II and insulin were proportionately less potent. In addition to its effect on proliferation, IGF-I also increased the number of 4E7- and GC-antigen positive cells. These observations indicate that oligodendrocytes in primary culture express specific IGF-I receptors and that the interaction of IGF-I with these receptors results in the proliferation as well as differentiation of oligodendrocytes.

    Original languageEnglish (US)
    Pages (from-to)117-131
    Number of pages15
    JournalRegulatory Peptides
    Volume33
    Issue number2
    DOIs
    StatePublished - Apr 25 1991

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    Keywords

    • Differentiation
    • Glial progenitor
    • IGF-I receptor
    • Multiplication
    • Oligodendrocyte

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology
    • Endocrinology
    • Clinical Biochemistry
    • Cellular and Molecular Neuroscience

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