期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 290, 期 5, 页码 H1777-H1787出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01087.2005
关键词
15-deoxy-Delta(12,14)-prostaglandin J(2); isoprostane; cyclopentenone; 4-hydroxynonenal; atherosclerosis; rho0
资金
- NCI NIH HHS [CA-77839] Funding Source: Medline
- NHLBI NIH HHS [HL-58013] Funding Source: Medline
- NIDDK NIH HHS [DK-48831] Funding Source: Medline
- NIEHS NIH HHS [ES-00267, ES-10167] Funding Source: Medline
- NIGMS NIH HHS [GM-15431] Funding Source: Medline
Electrophilic lipids, such as 4-hydroxynonenal (HNE), and the cyclopentenones 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and 15-J(2)-isoprostane induce both reactive oxygen species (ROS) formation and cellular antioxidant defenses, such as heme oxygenase-1 (HO-1) and glutathione (GSH). When we compared the ability of these distinct electrophiles to stimulate GSH and HO-1 production, the cyclopentenone electrophiles were somewhat more potent than HNE. Over the concentration range required to observe equivalent induction of GSH, dichlorofluorescein fluorescence was used to determine both the location and amounts of electrophilic lipid-dependent ROS formation in endothelial cells. The origin of the ROS on exposure to these compounds was largely mitochondrial. To investigate the possibility that the increased ROS formation was due to mitochondrial localization of the lipids, we prepared a novel fluorescently labeled form of the electrophilic lipid 15d-PGJ(2). The lipid demonstrated strong colocalization with the mitochondria, an effect which was not observed by using a fluorescently labeled nonelectrophilic lipid. The role of mitochondria was confirmed by using cells deficient in functional mitochondria. On the basis of these data, we propose that ROS formation in endothelial cells is due to the direct interaction of these lipids with the organelle.
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