Xyloketal B exhibits its antioxidant activity through induction of HO-1 in vascular endothelial cells and zebrafish.
Xyloketal B exhibits its antioxidant activity through induction of HO-1 in vascular endothelial cells and zebrafish.
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Xyloketal B 通过诱导血管内皮细胞和斑马鱼中的 HO-1 发挥抗氧化活性
DOI：
10.3390/md11020504
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发表时间：
2013-02-18
期刊：
影响因子：
5.4
通讯作者：
Guan YY
中科院分区：
文献类型：
--
作者：
Li ZX;Chen JW;Yuan F;Huang YY;Zhao LY;Li J;Su HX;Liu J;Pang JY;Lin YC;Lu XL;Pei Z;Wang GL;Guan YY
我们先前报道了一种新的海洋化合物，木缩酮B，在不同的心血管疾病模型中具有很强的抗氧化作用。血红素氧合酶-1（HO-1）是一种重要的内源性抗氧化酶，其诱导表达被认为是心血管疾病潜在的治疗策略。我们在此研究了木缩酮B是否通过诱导HO-1而表现出其抗氧化活性。在人脐静脉内皮细胞（HUVECs）中，木缩酮B以浓度和时间依赖性方式显著诱导HO-1基因表达和核因子-红细胞2相关因子2（Nrf-2）易位。木缩酮B对血管紧张素II诱导的细胞凋亡和活性氧（ROS）产生的保护作用可被HO-1特异性抑制剂锡原卟啉-IX（SnPP）消除。因此，SnPP可逆转木缩酮B对斑马鱼胚胎NADPH氧化酶活性的抑制作用。此外，木缩酮B以浓度和时间依赖性方式诱导Akt和Erk 1/2磷酸化。PI 3 K抑制剂LY 294002和Erk 1/2抑制剂U 0126可抑制木缩酮B诱导HO-1和Nrf-2转位，而P38抑制剂SB 203580则无此作用。综上所述，木缩酮B可通过PI 3 K/Akt/Nrf-2途径诱导HO-1的表达，而HO-1的诱导是木缩酮B抗氧化和抗凋亡作用的主要机制。
We previously reported that a novel marine compound, xyloketal B, has strong antioxidative actions in different models of cardiovascular diseases. Induction of heme oxygenase-1 (HO-1), an important endogenous antioxidant enzyme, has been considered as a potential therapeutic strategy for cardiovascular diseases. We here investigated whether xyloketal B exhibits its antioxidant activity through induction of HO-1. In human umbilical vein endothelial cells (HUVECs), xyloketal B significantly induced HO-1 gene expression and translocation of the nuclear factor-erythroid 2-related factor 2 (Nrf-2) in a concentration- and time-dependent manner. The protection of xyloketal B against angiotensin II-induced apoptosis and reactive oxygen species (ROS) production could be abrogated by the HO-1 specific inhibitor, tin protoporphyrin-IX (SnPP). Consistently, the suppressive effects of xyloketal B on NADPH oxidase activity could be reversed by SnPP in zebrafish embryos. In addition, xyloketal B induced Akt and Erk1/2 phosphorylation in a concentration- and time-dependent manner. Furthermore, PI3K inhibitor LY294002 and Erk1/2 inhibitor U0126 suppressed the induction of HO-1 and translocation of Nrf-2 by xyloketal B, whereas P38 inhibitor SB203580 did not. In conclusion, xyloketal B can induce HO-1 expression via PI3K/Akt/Nrf-2 pathways, and the induction of HO-1 is mainly responsible for the antioxidant and antiapoptotic actions of xyloketal B.
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影响因子：
2.9
作者：
Lu, Xi-lin;Yao, Xiao-li;Zeng, Jinsheng
通讯作者：
Zeng, Jinsheng
影响因子：
5.3
作者：
Chen, Jia-Shiong;Huang, Po-Hsun;Chen, Jaw-Wen
通讯作者：
Chen, Jaw-Wen
影响因子：
64.8
作者：
Dimmeler, S;Fleming, I;Zeiher, AM
通讯作者：
Zeiher, AM
影响因子：
4.8
作者：
Bouton, C;Demple, B
通讯作者：
Demple, B
影响因子：
2.8
作者：
Kim, Se-Jin;Park, Channy;Park, Raekil
通讯作者：
Park, Raekil