Insulin-like growth factor type 1 prevents hyperglycemia-induced uncoupling protein 3 down-regulation and oxidative stress
Insulin-like growth factor type 1 prevents hyperglycemia-induced uncoupling protein 3 down-regulation and oxidative stress
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DOI：
10.1002/jnr.20142
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发表时间：
2004-07-15
影响因子：
4.2
通讯作者：
Forsby, A
中科院分区：
文献类型：
--
作者：
Gustafsson, H;Söderdahl, T;Forsby, A
解偶联蛋白（UCPs）通过降低线粒体内膜电位（MMP）减少线粒体活性氧（ROS）的产生。我们以前已经表明，UCP 3的表达是积极调节胰岛素样生长因子-1（IGF-1）。本研究的目的是探讨UCPs在IGF-1介导的保护高血糖诱导的氧化应激和神经退行性变中的作用。人神经母细胞瘤SH-SY 5 Y细胞用视黄酸分化6天，之后开始暴露于8、30或60 mM葡萄糖，有或没有10 nM IGF-1。48-72小时后，检查每个细胞的神经突数量、UCP 3蛋白表达、MMP以及细胞内ROS和总谷胱甘肽水平。这些研究表明，葡萄糖浓度依赖性地减少了每个细胞的神经突的数量，在60 mM时减少了50%。同时，UCP 3蛋白表达下调，MMP升高了3.5倍，与8 mM葡萄糖孵育的细胞相比。此外，ROS水平增加，在60 mM葡萄糖下显示两倍最大值。这伴随着总谷胱甘肽水平的两倍升高，证实了细胞氧化还原状态的改变。IGF-1处理防止葡萄糖诱导的神经突变性和UCP 3下调。此外，MMP和ROS和谷胱甘肽的细胞内水平被归一化为对照细胞的那些。这些数据表明，IGF-1可能通过调节MMP，可能通过UCP 3的参与，保护免受高血糖诱导的氧化应激和神经元损伤。(C)2004 Wiley-Liss，Inc.
Uncoupling proteins (UCPs) have been reported to decrease the mitochondrial production of reactive oxygen species (ROS) by lowering the mitochondrial inner membrane potential (MMP). We have previously shown that UCP3 expression is positively regulated by insulin-like growth factor-1 (IGF-1). The aim of this study was to investigate the role of UCPs in IGF-1-mediated protection from hyperglycemia-induced oxidative stress and neurodegeneration. Human neuroblastoma SH-SY5Y cells were differentiated with retinoic acid for 6 days, after which exposure to 8, '30, or 60 mM glucose with or without 10 nM IGF-1 was started. After 48-72 hr, the number of neurites per cell, UCP3 protein expression, MMP, and intracellular levels of ROS and total glutathione were examined. These studies showed that glucose concentration-dependently reduced the number of neurites per cell, with a 50% reduction at 60 mM. In parallel, the UCP3 protein expression was down-regulated, and the MMP was raised 3.5-fold, compared with those in cells incubated with 8 mM glucose. Also, the ROS levels were increased, showing a twofold maximum at 60 mM glucose. This was accompanied by a twofold elevation of total glutathione levels, confirming an altered cellular redox state. IGF-1 treatment prevented the glucose-induced neurite degeneration and UCP3 downregulation. Furthermore, the MMP and the intracellular levels of ROS and glutathione were normalized to those of control cells. These data indicate that IGF-1 may protect from hyperglycemia-induced oxidative stress and neuronal injuries by regulating MMP, possibly by the involvement of UCP3. (C) 2004 Wiley-Liss, Inc.