DHEA-Bodipy-A functional fluorescent DHEA analog for live cell imaging

DHEA-Bodipy-A functional fluorescent DHEA analog for live cell imaging
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DOI:
10.1016/j.mce.2009.09.006
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发表时间:
2010-01-15
影响因子:
4.1
通讯作者:
Gehrig-Burger, Katja
Gehrig-Burger, Katja
中科院分区:
医学2区
文献类型:
--
作者:
Lemcke, Susanne;Hoennscheidt, Christoph;Gehrig-Burger, Katja

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雄激素脱氢表雄酮(DHEA)已被报道可以保护神经细胞免受功能障碍和凋亡。已经描述了参与这些效应的几种信号通路,但对DHEA的细胞内运输知之甚少。我们描述了一种新型荧光DHEA类似物DHEA-Bodipy的设计、合成和表征。DHEA-Bodipy被证明是一种功能性DHEA衍生物:DHEA-Bodipy(i)诱导雌激素受体α介导的基因激活,(ii)保护PC 12大鼠嗜铬细胞瘤细胞免受血清剥夺诱导的凋亡,(iii)诱导SH-SY 5 Y人神经母细胞瘤细胞中的应力纤维和粘着斑接触。DHEA-Bodipy与活的PC 12细胞的质膜快速特异性结合。我们分析了DHEA-Bodipy在人神经母细胞瘤细胞中的代谢和运输。DHEA-Bodipy是第一个适用于细胞内DHEA运输和定位的活细胞成像的功能性荧光DHEA衍生物。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
The androgen dehydroepiandrosterone (DHEA) has been reported to protect neuronal cells against dysfunction and apoptosis. Several signaling pathways involved in these effects have been described but little is known about the intracellular trafficking of DHEA. We describe design, synthesis and characterization of DHEA-Bodipy, a novel fluorescent DHEA analog. DHEA-Bodipy proved to be a functional DHEA derivative: DHEA-Bodipy (i) induced estrogen receptor alpha-mediated gene activation, (ii) protected PC12 rat pheochromocytoma cells against serum-deprivation-induced apoptosis, and (iii) induced stress fibers and focal adhesion contacts in SH-SY5Y human neuroblastoma cells. DHEA-Bodipy bound rapidly and specifically to plasma membranes of living PC12 cells. We analyzed metabolism and trafficking of DHEA-Bodipy in human neuroblastoma cells. DHEA-Bodipy is the first functional fluorescent DHEA derivative suitable for live cell imaging of intracellular DHEA transport and localization. (C) 2009 Elsevier Ireland Ltd. All rights reserved.