Tetramethylpyrazine alleviates iron overload damage in vascular endothelium via upregulating DDAHII expression
Tetramethylpyrazine alleviates iron overload damage in vascular endothelium via upregulating DDAHII expression
复制标题
四甲基吡嗪通过上调 DDAHII 表达减轻血管内皮铁过载损伤
DOI：
10.1016/j.tiv.2020.104817
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发表时间：
2020
影响因子：
3.2
通讯作者：
Ming He
中科院分区：
文献类型：
--
作者：
Qing Zhou;Shuping Chen;Hongwei Li;Bin Yang;Tianpeng Chen;Tianhong Hu;Dong Yin;Huan He;Ming He
铁超载会导致血管内皮细胞损伤。它被认为与过量的活性氧物种(ROS)的产生有关。川芎素(TMP)是川芎的有效成分，通过抑制氧化应激和细胞凋亡的级联反应来保护多种细胞。然而，TMP是否能增加DDAHII活性和表达对抗铁超载所致的内皮细胞损伤，其保护机制尚未阐明。在本研究中，50μM右旋糖苷铁与25μM TMP共同作用于人脐静脉内皮细胞48 h，TMP可提高细胞存活率，降低乳酸脱氢酶活性，增强DDAHⅡ的表达和活性，增加p-eNOS/eNOS比值，增加NO含量，降低ADMA水平。TMP还显示出很强的抗氧化活性，抑制了ROS的产生和氧化应激。此外，TMP还可减轻线粒体膜电位损失，抑制线粒体膜通透性转换孔开放，减少铁超载诱导的细胞凋亡。而TMP的保护作用随着PAD/DDAHII-shRNA的加入而消失。TMP的抗铁超载作用与阳性对照组、ADMA竞争性底物L精氨酸或自由基清除剂依达拉奉相似。提示TMP通过ROS/ADMA/DDAHII/eNOS/NO途径减轻血管内皮细胞铁超载损伤。
Iron overload causes vascular endothelium damage. It has been thought to relate excessive reactive oxygen species (ROS) generation. Tetramethylpyrazine (TMP), an active ingredient ofLigusticum chuanxiongHort, protects various cells by inhibiting oxidative stress and cascade reaction of apoptosis. However, whether TMP can increase DDAHII activity and expression against endothelial cell damage induced by iron overload, and the protective mechanism has not been elucidated. In this study, 50 μM iron dextran and 25 μM TMP were used to co-treat HUVECs for 48 h. TMP could increase cell viability and decrease LDH activity, enhance DDAHII expression and activity, p-eNOS/eNOS ratio, NO content, and reduce ADMA level. TMP also showed a strong antioxidant activity with inhibited ROS generation and oxidative stress. Moreover, TMP attenuated mitochondrial membrane potential loss, inhibited mitochondrial permeability transition pore openness, and decreased apoptosis induced by iron overload. While mentioned above, the protective effects of TMP were abolished with the addition of pAD/DDAHII-shRNA. The effects of TMP against iron overload were similar to the positive control groups, L-arginine, a competitive substrate of ADMA, or edaravone, free radical scavenger. These results signify that TMP alleviated iron overload damage in vascular endothelium via ROS/ADMA/ DDAHII/eNOS/NO pathway.