Oxyradical stress increases the biosynthesis of 2-arachidonoylglycerol: involvement of NADPH oxidase

文献类型： 外文期刊

第一作者： Matthews, Anberitha T.

作者： Matthews, Anberitha T.;Lee, Jung Hwa;Borazjani, Abdolsamad;Mangum, Lee C.;Hou, Xiang;Ross, Matthew K.;Hou, Xiang

作者机构：

关键词： 2-arachidonoylglycerol;macrophages;NADPH oxidase;atherosclerosis;endocannabinoids

期刊名称：AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY （ 影响因子：4.249； 五年影响因子：4.627 ）

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收录情况： SCI

摘要： NADPH oxidase (Nox)-derived oxyradicals contribute to atherosclerosis by oxidizing low-density lipoproteins (LDL), leading to their phagocytosis by vascular macrophages. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG), might be an important link between oxidative stress and atherosclerosis. We hypothesized that 2-AG biosynthesis in macrophages is enhanced following ligation of oxidized LDL by scavenger receptors via a signal transduction pathway involving Nox-derived ROS that activates diacylglycerol lipase-beta (DAGL-beta), the 2-AG biosynthetic enzyme. To test this idea, we challenged macrophage cell lines and murine primary macrophages with a xanthine oxidase system or with nonphysiological and physiological Nox stimulants [phorbol 12-my-ristate 13-acetate (PMA) and arachidonic acid (AA)]. Each stressor increased cellular superoxide levels and enhanced 2-AG biosynthetic activity in a Nox-dependent manner. Levels of cytosolic phospho-lipase A_2-dependent AA metabolites (eicosanoids) in primary macrophages were also dependent on Nox-mediated ROS. In addition, 2-AG levels in DAGL-beta-overexpressing COS7 cells were attenuated by inhibitors of Nox and DAGL-beta. Furthermore, ROS induced by men-adione (a redox cycling agent) or PMA could be partially attenuated by the cannabinoid 1/2 receptor agonist (WIN 55,212-2). Finally, cells that overexpress Nox2 components (Phox-COS7) synthesized larger amounts of 2-AG compared with the parental COS7 cells. Together, the results suggest a positive correlation between heightened oxygen radical flux and 2-AG biosynthesis in macrophage cell lines and primary macrophages. Because of the antioxidant and anti-inflammatory effects associated with 2-AG, the increased levels of this bioae-tive lipid might be an adaptive response to oxidative stress. Thus oxyradical stress may be counteracted by the enhanced endocannabi-noid tone.

分类号： R33

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