Zheng Kun-mu, Zhang Jing, Zhang Cui-lin, Zhang Yun-wu, Chen Xiao-chun
Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou 350001, China.
1] Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou 350001, China [2] Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350001, China.
Acta Pharmacol Sin. 2015 May;36(5):544-52. doi: 10.1038/aps.2014.166. Epub 2015 Apr 20.
Appoptosin (SLC25A38) is a pro-apoptotic protein, which is upregulated in Alzheimer's disease (AD) brains and plays an important role in promoting the pathological progress of AD. The aim of this study was to investigate the effects of curcumin from the rhizome of Curcuma longa on appoptosin-induced apoptosis in SH-SY5Y cells.
SH-SY5Y cells were pretreated with curcumin, then transfected with appoptosin or vector. The apoptotic cells were detected with Annexin V staining analysis by flow cytometry. The expression of cleaved caspase-3, appoptosin, heme oxygenase-1 (HO-1) was examined using Western blotting. Intracellular level of ROS was measured with DCFH-DA staining by flow cytometry analysis. Mitochondrial membrane potential (ΔΨm) was detected with JC-1 staining under a fluorescence microscope and quantified by fluorescence ratio detection.Overexpression of appoptosin in SH-SY5Y cells markedly increased cell apoptosis accompanied by reduced HO-1 expression, increased intracellular heme level, ROS overproduction and ΔΨm impairment. Treatment of SH-SY5Y cells with curcumin (2.5-20 μmol/L) for 24 h did not significantly affect their viability. However, pretreatment with curcumin (2.5-20 μmol/L) dose-dependently attenuated all above-mentioned pathological changes in appoptosin-transfected SH-SY5Y cells.
Overexpression of appoptosin in SH-SY5Y cells markedly increased cell apoptosis accompanied by reduced HO-1 expression, increased intracellular heme level, ROS overproduction and ΔΨm impairment. Treatment of SH-SY5Y cells with curcumin (2.5-20 μmol/L) for 24 h did not significantly affect their viability. However, pretreatment with curcumin (2.5-20 μmol/L) dose-dependently attenuated all above-mentioned pathological changes in appoptosin-transfected SH-SY5Y cells.
Curcumin inhibits appoptosin-induced apoptosis in SH-SY5Y cells by upregulating the expression of HO-1, reducing the production of intracellular heme and ROS, and preventing the ΔΨm loss.
凋亡素（SLC25A38）是一种促凋亡蛋白，在阿尔茨海默病（AD）脑内表达上调，在促进AD病理进程中起重要作用。本研究旨在探讨姜黄根茎中的姜黄素对凋亡素诱导的SH-SY5Y细胞凋亡的影响。
用姜黄素预处理SH-SY5Y细胞，然后转染凋亡素或载体。通过流式细胞术用膜联蛋白V染色分析检测凋亡细胞。用蛋白质免疫印迹法检测裂解的半胱天冬酶-3、凋亡素、血红素加氧酶-1（HO-1）的表达。通过流式细胞术分析用DCFH-DA染色测量细胞内活性氧水平。在荧光显微镜下用JC-1染色检测线粒体膜电位（ΔΨm），并通过荧光比率检测进行定量。凋亡素在SH-SY5Y细胞中的过表达显著增加细胞凋亡，同时伴有HO-1表达降低、细胞内血红素水平升高、活性氧过度产生和ΔΨm损伤。用姜黄素（2.5 - 20μmol/L）处理SH-SY5Y细胞24小时对其活力没有显著影响。然而，用姜黄素（2.5 - 20μmol/L）预处理剂量依赖性地减轻了凋亡素转染的SH-SY5Y细胞中上述所有病理变化。
凋亡素在SH-SY5Y细胞中的过表达显著增加细胞凋亡，同时伴有HO-1表达降低、细胞内血红素水平升高、活性氧过度产生和ΔΨm损伤。用姜黄素（2.5 - 20μmol/L）处理SH-SY5Y细胞24小时对其活力没有显著影响。然而，用姜黄素（2.5 - 20μmol/L）预处理剂量依赖性地减轻了凋亡素转染的SH-SY5Y细胞中上述所有病理变化。
姜黄素通过上调HO-1的表达、减少细胞内血红素和活性氧的产生以及防止ΔΨm丧失来抑制凋亡素诱导的SH-SY5Y细胞凋亡。
