Delphinidin-3-glucoside protects against oxidized low-density lipoprotein-induced mitochondrial dysfunction in vascular endothelial cells via the sodium-dependent glucose transporter SGLT1.
Delphinidin-3-glucoside protects against oxidized low-density lipoprotein-induced mitochondrial dysfunction in vascular endothelial cells via the sodium-dependent glucose transporter SGLT1.
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Delphinidin-3-Glucoside 通过钠依赖性葡萄糖转运蛋白 SGLT1 防止血管内皮细胞氧化低密度脂蛋白诱导的线粒体功能障碍
DOI：
10.1371/journal.pone.0068617
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mi MT
中科院分区：
文献类型：
--
作者：
Jin X;Yi L;Chen ML;Chen CY;Chang H;Zhang T;Wang L;Zhu JD;Zhang QY;Mi MT
飞雀素-3-葡萄糖苷(DP)是花青素家族中的一员，这种化合物天然存在于有色植物中，已知可以缓解氧化应激。先前的研究表明，DP可降低血管内皮细胞的氧化应激，然而，其潜在的机制仍不清楚。在本研究中，我们发现DP可显著抑制氧化型低密度脂蛋白(OxLDL)诱导的原代人脐静脉内皮细胞(HUVECs)增殖抑制和细胞凋亡。此外，DP通过减少活性氧(ROS)和超氧阴离子的产生，从而抑制线粒体膜电位，关闭线粒体通透性转换孔，从而减轻oxLDL诱导的线粒体功能障碍。此外，体外和体内数据表明，DP通过钠依赖的葡萄糖转运体(SGLT1)以温度、浓度和时间依赖的方式转运到内皮细胞。SGLT1的底物葡萄糖、其抑制剂根茎苷或SGLT1的siRNA抑制了DP的转运。抑制SGLT1可显著抑制促凋亡因子(凋亡诱导因子、细胞色素c、Caspase-3和Bax/Bcl-2)诱导的线粒体功能紊乱的DP功能。综上所述，我们的数据表明DP通过SGLT1-ROS-线粒体通路保护血管内皮细胞。这一新的见解可能有助于阐明在预防内皮功能障碍和动脉粥样硬化的背景下，DP和花青素提供的血管保护的分子机制。
Delphinidin-3-glucoside (Dp) is a member of a family of bioactive compounds known as anthocyanins that occur naturally in pigmented plants and are known to ameliorate oxidative stress. Previous studies have showed that Dp decreased oxidative stress in vascular endothelial cells, however, the underlying mechanisms remain largely unknown. In the present study, we showed that pretreatment with Dp significantly suppressed oxidized low-density lipoprotein (oxLDL)-induced cell proliferation inhibition and apoptosis in primary human umbilical vein endothelial cells (HUVECs). Also, Dp pretreatment attenuated oxLDL-induced mitochondrial dysfunction via decreased reactive oxygen species (ROS) and superoxide anion generation, thereby repressing mitochondrial membrane potential and closing mitochondrial permeability transition pore. Furthermore, in vitro and in vivo data showed that Dp was transported into endothelial cells in a temperature, concentration, and time-dependent manner via the sodium-dependent glucose transporter (SGLT1). Suppression of SGLT1 by its substrate glucose, its inhibitor phlorizin or SGLT1 siRNA blocked Dp transportation. Repression of SGLT1 significantly inhibited Dp function of ameliorating mitochondrial dysfunction induced by pro-apoptotic factors (Apoptosis-inducing factor, Cytochrome c, Caspase-3 and Bax/Bcl-2 ratio). Taken together, our data indicate that Dp protects VECs via the SGLT1-ROS-mitochodria pathway. This new insight may help to elucidate the molecular mechanisms underlying the vascular protection afforded by Dp, and anthocyanins in general, in the context of prevention of endothelial dysfunction and atherosclerosis.
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影响因子：
2.6
作者：
Chen, Chun-ye;Yi, Long;Yu, Bin
通讯作者：
Yu, Bin
DOI：
10.1152/ajpendo.00005.2010
发表时间：
2010-09-01
影响因子：
5.1
作者：
Liu, Shu;Shen, Hua;Du, Jie
通讯作者：
Du, Jie
影响因子：
8.4
作者：
Cooke, D;Steward, WP;Marczylo, T
通讯作者：
Marczylo, T
影响因子：
9.7
作者：
Chen, Pei-Ni;Chu, Shu-Chen;Hsieh, Yih-Shou
通讯作者：
Hsieh, Yih-Shou
影响因子：
4.7
作者：
Lazzè, MC;Savio, M;Bianchi, L
通讯作者：
Bianchi, L