Abstract
This study was designed to investigate a possible role of the N-terminal tripeptide of insulin-like growth factor-1 (IGF-I), Gly-Pro-Glu (GPE), physiologically generated in neurons following IGF-I-specific cleavage, in promoting neural regeneration after an injury. Primary cultures of mouse neural stem cells (NSCs), obtained from 13.5 Days post-conception (dpc) mouse embryos, were challenged with either GPE, growth hormone (GH), or GPE + GH and the effects on cell proliferation, migration, and survival were evaluated both under basal conditions and in response to a wound healing assay. The cellular pathways activated by GPE were also investigated by using specific chemical inhibitors. The results of the study indicate that GPE treatment promotes the proliferation and the migration of neural stem cells in vitro through a mechanism that involves the activation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase PI3K-Akt pathways. Intriguingly, both GPE effects and the signaling pathways activated were similar to those observed after GH treatment. Based upon the results obtained from this study, GPE, as well as GH, may be useful in promoting neural protection and/or regeneration after an injury.
Highlights
Besides its role as a critical mediator of body growth and development [1,2], the insulin-like growth factor-1 (IGF-1) plays a prominent role in central nervous system (CNS) development and metabolism
Cell Proliferation Induced by Gly-Pro-Glu (GPE) or Growth Hormone (GH) Treatment of primary neural stem cells (NSCs) cultures with 100 μM Glu tripeptide (GPE) induced a significant increase in the number of BrdU+Trceealtlmsy
Administration of GPE protects neurons from NMDA-induced toxicity rat cortical slices, while central administration of GPE reduces the extent of cortical infarction in several models of hypoxia-ischemia in rats [15,16,17,18,29]
Summary
Besides its role as a critical mediator of body growth and development [1,2], the insulin-like growth factor-1 (IGF-1) plays a prominent role in central nervous system (CNS) development and metabolism. IGF-1 continues to exert a prominent role in regulating many CNS functions including neuromodulation, neuroprotection, neural plasticity, and neural repair [4,5,6,7]. Owing to these actions, IGF-1 has been proposed as a novel therapeutic in several neurological disorders, its clinical application is limited by its large molecular size, poor central uptake, and mitogenic potential. Cell Proliferation Induced by Gly-Pro-Glu (GPE) or Growth Hormone (GH) Treatment of primary NSC cultures with 100 μM GPE induced a significant increase in the number of BrdU+Trceealtlms (eFnitguofrep2riAm,Bar)y.
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