Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.4.37 (
CNPase
)
539
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Insulin-like growth factor-1 (IGF-1) is a growth and survival factor for oligodendrocyte lineage cells and induces myelination. Its actions are modulated by IGF binding proteins (IGFBPs) that are present in the extracellular fluids or on the cell surface. Additionally, IGFBPs are also known to exert actions that are independent of IGF-1. We studied whether IGF-binding proteins (IGFBPs)-1 and -2 modulate rat oligodendrocyte precursor (O2A) cell survival and differentiation in vitro both in the absence and presence of exogenously added IGF-1. The data reveal that
IGFBP-1
and -2 reduced O2A cell survival in the absence and presence of exogenously added IGF-1. The effects of
IGFBP-1
on cell survival in the presence of exogenously added IGF-1 were IGF-1-dependent, whereas IGFBP-2 displayed both IGF-1-dependent and IGF-1-independent effects. Furthermore,
IGFBP-1
and -2 inhibited O2A cell differentiation in the presence of IGF-1 as reflected by decreased expression levels of two myelin proteins,
CNPase
(
2',3'-cyclic nucleotide 3'-phosphohydrolase
) and MAG (myelin associated glycoprotein). Analysis of medium samples revealed that O2A cells do not secrete proteases that degrade these IGFBPs. Taken together the data show that
IGFBP-1
and -2 are negative effectors of oligodendrocyte survival and differentiation. Accordingly, the role of IGFBPs should be explicitly taken into account when investigating IGF-1 effects on oligodendrocytes, especially in the context of therapeutic purposes.
...
PMID:Insulin-like growth factor binding proteins-1 and -2 differentially inhibit rat oligodendrocyte precursor cell survival and differentiation in vitro. 1211 2
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.
...
PMID:Insulin-like growth factor binding protein-1 activates integrin-mediated intracellular signaling and migration in oligodendrocytes. 2034 50
