Reactive oxygen species production by BP-1,6-quinone and its effects on the endothelial dysfunction: Involvement of the mitochondria.
Strong epidemiological evidence supports the association between increased air pollution and the risk of developing atherosclerotic cardiovascular diseases (CVDs). However, the mechanism remains unclear. As an environmental air pollutant and benzo-a-pyrene (BP) metabolite, BP-1,6-quinone (BP-1,6-Q) is present in the particulate phase of air pollution. This study was undertaken to examine the redox activity of BP-1,6-Q and mechanisms associated with it using EA.hy926 endothelial cells. BP-1,6-Q at 0.01-1 μM significantly stimulated the production of reactive oxygen species (ROS)·in intact cells and isolated mitochondria. Furthermore, BP-1,6-Q-induced ROS was altered by mitochondrial electron transport chain (METC) inhibitors of complex I (rotenone) and complex III (antimycin A), denoting the involvement of mitochondrial electron transport chain (METC) in BP-1,6-Q mediated ROS production. In METC deficient cells, interestingly, BP-1,6-Q-mediated ROS production was enhanced, suggesting that overproduction of ROS by BP-1,6-Q is not only produced from mitochondria but can also be from the cell outside of mitochondria (extramitochondrial). BP-1,6-Q also triggered endothelial-monocyte interaction and stimulated expression of vascular adhesion molecule-1 (VCAM-1). In conclusion, these results demonstrate that BP-1,6-Q can generate ROS within both mitochondria and outside of mitochondria, resulting in stimulation of adhesion of monocytes to endothelial cells, a key event in the pathogenesis of atherosclerosis.
['Shukla|Halley|H|', 'Chitrakar|Rojin|R|', 'Bibi|Humaira A|HA|', 'Gaje|Gabriella|G|', 'Koucheki|Ashkon|A|', 'Trush|Michael A|MA|', 'Zhu|Hong|H|', 'Li|Y Robert|YR|', 'Jia|Zhenquan|Z|']
D001580:Benzopyrenes D002448:Cell Adhesion D002460:Cell Line D018920:Coculture Techniques D045222:Electron Transport Chain Complex Proteins D042783:Endothelial Cells D006801:Humans D008928:Mitochondria D009000:Monocytes D010084:Oxidation-Reduction D018384:Oxidative Stress D017382:Reactive Oxygen Species D015398:Signal Transduction D019010:Vascular Cell Adhesion Molecule-1
BP-1,6-quinone Cardiovascular diseases Mitochondrial electron transport chain Hydrogen peroxide Inflammation Particulate matter Superoxide Vascular adhesion molecule