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KMID : 0613820110210070961
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Journal of Life Science
2011 Volume.21 No. 7 p.961 ~ p.968
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4-Hydroxynonenal Induces Endothelial Cell Apoptosis via ROS and Peroxynitrite Generation
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Chung Sang-Won
Yee Su-Bog
Lee Ji-Young
Hossain Mohammad Akbar
Kim Dong-Hwan
Yoon Jeong-Hyun
Chung Hae-Young
Kim Nam-Deuk
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Abstract
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The formation of reactive lipid aldehydes, 4-hydroxynonenal (HNE) is shown to be derived from fatty acid hydroperoxides through the oxidative process. Among its known effects in cytotoxicity, HNE has been implicated in apoptotic cell death. To delineate its putative role as a potential mediator, we investigated the mechanism by which HNE induces apoptosis of endothelial cells (ECs). The anti-proliferative effects of HNE were tested through MTT assay after exposure to various concentrations (5~15 μM) of HNE. We observed apoptotic bodies with propidium iodide staining, and measured the HNE induction of endothelial apoptosis by flow cytometry assay. We observed that cells exposed to HNE for 24 hr resulted in increased poly(ADP-ribose) polymerase cleavage and up-regulation of Bax. Data on the HNE action strongly indicated the involvement of reactive species, namely, intracellular ROS, nitrite, and peroxynitrite. To obtain evidence on the implication of ROS and peroxynitrite in HNE-induced apoptosis, a ROS scavenger, N-acetylcysteine (NAC), and a peroxynitrite scavenger, penicillamine, were tested. Results clearly indicate that the induction of apoptosis by HNE was effectively inhibited by NAC and penicillamine. Based on the present data, we conclude that the endothelial apoptosis induced by HNE involves both ROS generation and peroxynitrite activity. Our new data could lead to a redefinition of HNE action on apoptosis in ECs.
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KEYWORD
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4-Hydroxynonenal, apoptosis, ROS, peroxynitrite, endothelial cells
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