Protective Effects of a Synthesized Butyrolactone Derivative against Chloroquine-Induced Autophagic Vesicle Accumulation and the Disturbance of Mitochondrial Membrane Potential and Na+,K+-ATPase Activity in Vascular Endothelial Cells
Protective Effects of a Synthesized Butyrolactone Derivative against Chloroquine-Induced Autophagic Vesicle Accumulation and the Disturbance of Mitochondrial Membrane Potential and Na+,K+-ATPase Activity in Vascular Endothelial Cells
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DOI：
10.1021/tx8002824
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发表时间：
2009-03-01
影响因子：
4.1
通讯作者：
Miao, JunYing
中科院分区：
文献类型：
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作者：
Huang, Bin;Meng, Ning;Miao, JunYing
我们先前发现丁内酯衍生物3-苄基-5-（（2-硝基苯氧基）甲基）-二氢呋喃-2（3 H）-酮（3BDO）可以抑制由血清和FGF-2剥夺诱导的血管内皮细胞（VEC）凋亡和衰老。本研究旨在探讨其在氯喹（CQ）诱导的VEC自噬中的作用。通过测定酸性区室容积（VAC）和吖啶橙子（AO）染色及微管相关蛋白I轻链3（MAP 1 LC 3）法分析自噬，发现3BDO能有效抑制CQ诱导的VECs自噬囊泡积聚（空泡化）。用5，5 '，6，6'-四氯-1，1 '，3，3'-四乙基苯并咪唑基碘化花青（JC-1）测定线粒体膜电位（MMP）。结果表明，CQ可显著升高MMP，3BDO可显著抑制CQ诱导的MMP升高。Na+，K+-ATP酶活性测定表明，CQ对该酶活性有明显的抑制作用，3BDO可减弱CQ引起的Na+，K+-ATP酶活性的变化。结论：3BDO能有效抑制CQ诱导的VECs自噬囊泡的形成，并能减弱CQ诱导的MMP和Na+，K+-ATP酶活性的变化。这些数据表明，3BDO，将是一个潜在的工具，研究自噬的机制。
We previously found a butyrolactone derivative, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO), could inhibit vascular endothelial cell (VEC) apoptosis and senescence induced by a deprivation of serum and FGF-2. In this study, we aimed to investigate its actions in VEC autophagy induced by chloroquine (CQ). The measurement on the volume of acidic compartments (VAC) and autophagy analysis by acridine orange (AO) staining and microtubule-associated protein I light chain 3 (MAP1LC3) process revealed that 3BDO was an effective inhibitor of autophagic vesicle accumulation (vacuolation) induced by CQ in VECs. 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylearbocyanine iodide (JC-1) was used for mitochondrial rnembrane potential (MMP) measurement. The results showed that CQ elevated MMP significantly and that 3BDO could significantly inhibit CQ-induced MMP increase. Na+,K+-ATPase activity assay showed that CQ inhibited this enzyme activity significantly and that 3BDO attenuated the alteration of Na+,K+-ATPase activity caused by CQ. We concluded that 3BDO was a promising inhibitor of CQ-induced accumulation of autophagic vesicles in VECs and could weaken the alterations of MMP and Na+,K+-ATPase activity induced by CQ. The data indicate that 3BDO, will be a potential tool for investigating the mechanism of autophagy.