Insulin-like growth factor-I-stimulated Akt phosphorylation and oligodendrocyte progenitor cell survival require cholesterol-enriched membranes.
Insulin-like growth factor-I-stimulated Akt phosphorylation and oligodendrocyte progenitor cell survival require cholesterol-enriched membranes.
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DOI：
10.1002/jnr.22099
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发表时间：
2009-11-15
影响因子：
4.2
通讯作者：
Wood TL
中科院分区：
文献类型：
--
作者：
Romanelli RJ;Mahajan KR;Fulmer CG;Wood TL
Previously we showed that insulin-like growth factor-I (IGF-I) promotes sustained phosphorylation of Akt in oligodendrocyte progenitor cells (OPCs) and that Akt phosphorylation is required for survival of these cells. The direct mechanisms, however, by which IGF-I promotes Akt phosphorylation are currently undefined. Recently, cholesterol-enriched membranes (CEMs) have been implicated in regulation of growth factor-mediated activation of the PI3K/Akt pathway and survival of mature oligodendrocytes; however, less is know about their role in OPC survival. In the present study, we investigate the role of CEMs in IGF-I-mediated Akt phosphorylation and OPC survival. We report that acute disruption of membrane cholesterol with methyl-β-cyclodextrin results in altered OPC morphology and inhibition of IGF-I-mediated Akt phosphorylation. We also report that long-term inhibition of cholesterol biosynthesis with 25-hydroxycholesterol blocks IGF-I stimulated Akt phosphorylation and cell survival. Moreover, we show that the PI3K regulatory subunit, p85, Akt, and the IGF-IR are sequestered within cholesterol-enriched fractions in steady-state stimulation of the IGF-IR and that phosphorylated Akt and IGF-IR are present in cholesterol-enriched fractions with IGF-I stimulation. Together, the results of these studies support a role for CEMs or “lipid rafts” in IGF-I-mediated Akt phosphorylation and provide a better understanding of the mechanisms by which IGF-I promotes OPC survival.
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影响因子：
9.2
作者：
Baron, W;Decker, L;ffrench-Constant, C
通讯作者：
ffrench-Constant, C
影响因子：
4.8
作者：
Matthews, LC;Taggart, MJ;Westwood, M
通讯作者：
Westwood, M
影响因子：
5.3
作者：
Decker, L;ffrench-Constant, C
通讯作者：
ffrench-Constant, C
影响因子：
3.5
作者：
Frederick, TJ;Wood, TL
通讯作者：
Wood, TL
DOI：
10.1073/pnas.89.5.1894
发表时间：
1992-03-01
影响因子：
11.1
作者：
KOMOLY, S;HUDSON, LD;BONDY, CA
通讯作者：
BONDY, CA