Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish
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 cardiovascu...
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doaj-19f08daeda454889bc508f5560454b492020-11-24T22:55:59ZengMDPI AGMarine Drugs1660-33972013-02-0111250452210.3390/md11020504Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and ZebrafishGuan-Lei WangXi-Lin LuZhong PeiYong-Cheng LinJi-Yan PangHuan-Xing SuJie LiuYun-Ying HuangJie LiLi-Yan ZhaoJian-Wen ChenFeng YuanYong-Yuan GuanZhen-Xing LiWe 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.http://www.mdpi.com/1660-3397/11/2/504xyloketal Bapoptosisreactive oxygen speciesHO-1Nrf-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guan-Lei Wang Xi-Lin Lu Zhong Pei Yong-Cheng Lin Ji-Yan Pang Huan-Xing Su Jie Liu Yun-Ying Huang Jie Li Li-Yan Zhao Jian-Wen Chen Feng Yuan Yong-Yuan Guan Zhen-Xing Li |
spellingShingle |
Guan-Lei Wang Xi-Lin Lu Zhong Pei Yong-Cheng Lin Ji-Yan Pang Huan-Xing Su Jie Liu Yun-Ying Huang Jie Li Li-Yan Zhao Jian-Wen Chen Feng Yuan Yong-Yuan Guan Zhen-Xing Li Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish Marine Drugs xyloketal B apoptosis reactive oxygen species HO-1 Nrf-2 |
author_facet |
Guan-Lei Wang Xi-Lin Lu Zhong Pei Yong-Cheng Lin Ji-Yan Pang Huan-Xing Su Jie Liu Yun-Ying Huang Jie Li Li-Yan Zhao Jian-Wen Chen Feng Yuan Yong-Yuan Guan Zhen-Xing Li |
author_sort |
Guan-Lei Wang |
title |
Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish |
title_short |
Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish |
title_full |
Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish |
title_fullStr |
Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish |
title_full_unstemmed |
Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish |
title_sort |
xyloketal b exhibits its antioxidant activity through induction of ho-1 in vascular endothelial cells and zebrafish |
publisher |
MDPI AG |
series |
Marine Drugs |
issn |
1660-3397 |
publishDate |
2013-02-01 |
description |
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. |
topic |
xyloketal B apoptosis reactive oxygen species HO-1 Nrf-2 |
url |
http://www.mdpi.com/1660-3397/11/2/504 |
work_keys_str_mv |
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