1. Insulin-like growth factor-binding protein 6 inhibits survival and differentiation of rat oligodendrocyte precursor cells
- Author
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Kuhl, NM, Hoekstra, D, De Vries, H, De Keyser, J, Gerontology, and Nanotechnology and Biophysics in Medicine (NANOBIOMED)
- Subjects
FACTOR-BINDING-PROTEIN ,mRNA ,Cell Differentation/physiology ,Insulin-Like-Growth-Factor-Binding Protein ,SELECTIVE AFFINITY ,myelin proteins ,survival ,Myelin-Assoc. Glycoprotein/antagonists ,CEREBROSPINAL-FLUID ,2',3'-Cyclic-Nucleotide Phosphodiesterases/antagon ,GROWTH-FACTOR-I ,HUMAN NEUROBLASTOMA-CELLS ,Animals ,O2A cells ,Cell survival/physiology ,GENE-EXPRESSION ,des(1-3)-IGF-1 ,Cultured ,6/biosynthesis/genetics/physiology ,CENTRAL-NERVOUS-SYSTEM ,Developmental/physiology ,IGF-I ,Gene Expression Regulation ,EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS ,FACTOR (IGF)-BINDING PROTEINS ,inhibitors/biosynthesis ,CELLS ,Growth Inhibitors/biosynthesis/genetics/physiology - Abstract
Insulin-like growth factor 1 (IGF-1) is a growth and survival factor for oligodendrocyte lineage cells and promotes myelination. We demonstrate that IGF-binding protein 6 (IGFBP-6) is expressed and localized to the Golgi complex in rat oligodendrocyte precursor (O2A) cells. IGFBP-6 mRNA showed a developmentally regulated expression pattern, displaying a transient decrease during early development, and enhanced levels upon cell maturation. IGFBP-6 mRNA expression could be reduced by addition of basic fibroblast growth factor and progesterone while estrogen increased IGFBP-6 mRNA. IGF-1, platelet-derived growth factor, and insulin had no effect. When added exogenously, IGFBP-6 reduced O2A cell survival in the absence of IGF-1 and inhibited IGF-1-stimulated survival in a partially IGF-1-dependent and partially IGF-1-independent fashion. In addition, IGFBP-6 reduced the IGF-stimulated expression of two myelin proteins, CNPase and MAG. Taken together, the data show that IGFBP-6 is a new negative effector of oligodendrocyte survival and differentiation. Copyright 2003 Wiley-Liss, Inc.
- Published
- 2003