Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.37 (CNPase)
 539 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IGF-1 is an important factor for myelin synthesis and hence possesses therapeutic potential in treating demyelinating disease such as multiple sclerosis. However, IGF-1 poorly crosses the blood-brain barrier. In this study, we investigated the effects of the sex steroid progesterone and the glucocorticoid dexamethasone on regulation of the IGF-system in glial cells. By means of quantitative PCR analysis, we demonstrate that progesterone upregulates IGF-1, the type 1 IGF receptor and IGFBP-2 in primary rat astrocytes and both IGF-1 and IGFBP-6 in OLN-93 oligodendroglial progenitor cells. In contrast, dexamethasone showed a negative effect on expression of IGF-1, the type 1 IGF receptor and the respective IGF binding proteins in both cell types. In oligodendrocytes, the differentiation marker CNPase was positively regulated by progesterone and negatively regulated by dexamethasone. Further, oligodendroglial cell migration was enhanced approximately 4-fold by progesterone. This study implicates progesterone as a positive regulator of IGF-system in glial cells and demonstrates a further biological function of progesterone in oligodendrocyte biology, namely stimulation of progenitor cell migration. Dexamethasone, on the other hand, is a negative regulator of the IGF-system in glial cells.
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PMID:Progesterone and dexamethasone differentially regulate the IGF-system in glial cells. 1985 40

In multiple sclerosis (MS), oligodendrocytes in lesions are lost, leaving damaged tissue virtually devoid of these myelin-producing cells. Our group has recently demonstrated enhanced expression of insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) in oligodendrocytes (CNPase(+)) localized adjacent to MS lesions. In the present study, we demonstrate IGF-1-independent actions of IGFBP-1 on OLN-93 oligodendroglial cells, including activation of kinases ERK1/2, focal adhesion kinase and p21-activated kinase as well as small monomeric GTPases Rac and Ral. Activation of these intracellular signaling components was inhibited by GRGDS peptide, indicating signaling through integrin receptors. While both IGF-1 and IGFBP-1 demonstrated rapid induction of actin polymerization, IGFBP-1 proved to be a more potent inducer of migration than IGF-1, inducing a threefold increased migration rate. Furthermore, through integrin receptor signaling IGFBP-1 induced rapid transient translocalization of intracellular Rac toward punctuated structures followed by translocation of Rac to the plasma membrane. Our results suggest that up-regulation of IGFBP-1 in oligodendrocytes in MS may serve two functions: (i) regulate IGF-1 actions, (ii) exert IGF-independent effects through its RGD sequence.
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PMID:Insulin-like growth factor binding protein-1 activates integrin-mediated intracellular signaling and migration in oligodendrocytes. 2034 50