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Brain Res. 2012 Jan 9;1430:18-24. doi: 10.1016/j.brainres.2011.10.046. Epub 2011 Nov 4.

IGF-1 induces hypoxia-inducible factor 1α-mediated GLUT3 expression through PI3K/Akt/mTOR dependent pathways in PC12 cells.

Author information

1
Department of Neurosurgery, The Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.

Abstract

Glucose metabolism is essential for most mammalian neurons, and the passage of glucose across cell membranes is mainly facilitated by glucose transporter 3 (GLUT3). In ischemia/reperfusion injured brains, increase of IGF-1 secretion and GLUT3 up-regulation, are regarded as protective processes. Recent works have shown that various growth factors and cytokines including IGF-1 can stimulate HIF-1α expression, thereby triggering transcription of numerous hypoxia-inducible genes by oxygen-independent mechanisms. So, we hypothesized that HIF-1α might play important role in the process of IGF-1 induced GLUT3. Using echinomycin, a HIF-1 inhibitor, and HIF-1α siRNA, we demonstrated IGF-1 induced GLUT3 expression through HIF-1α in neuronal PC12 cells. Moreover, IGF-1 stimulated HIF-1α and GLUT3 protein expression through phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR dependent pathways. Analysis of GLUT3 promoter deletion sequences indicated that a putative hypoxia-response element (HRE) was critical in GLUT3 promoter activity when PC12 cells were treatment with CoCl(2) and IGF-1. In conclusion, we showed that the expression of GLUT3 in response to IGF-1 was dependent on PI-3-kinase and mTOR activity, and required the transcription factor HIF-1α.

PMID:
22104347
DOI:
10.1016/j.brainres.2011.10.046
[Indexed for MEDLINE]

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