血管紧张素II - AT1受体刺激细胞核内的活性氧。
The angiotensin II-AT1 receptor stimulates reactive oxygen species within the cell nucleus.
作者信息
Pendergrass Karl D, Gwathmey Tanya M, Michalek Ryan D, Grayson Jason M, Chappell Mark C
机构信息
The Hypertension and Vascular Research Center, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
出版信息
Biochem Biophys Res Commun. 2009 Jun 26;384(2):149-54. doi: 10.1016/j.bbrc.2009.04.126. Epub 2009 May 3.
Abstract
We and others have reported significant expression of the Ang II Type 1 receptor (AT1R) on renal nuclei; thus, the present study assessed the functional pathways and distribution of the intracellular AT1R on isolated nuclei. Ang II (1nM) stimulated DCF fluorescence, an intranuclear indicator of reactive oxygen species (ROS), while the AT1R antagonist losartan or the NADPH oxidase (NOX) inhibitor DPI abolished the increase in ROS. Dual labeling of nuclei with antibodies against nucleoporin 62 (Nup62) and AT1R or the NADPH oxidase isoform NOX4 revealed complete overlap of the Nup62 and AT1R (99%) by flow cytometry, while NOX4 was present on 65% of nuclei. Treatment of nuclei with a PKC agonist increased ROS while the PKC inhibitor GF109203X or PI3 kinase inhibitor LY294002 abolished Ang II stimulation of ROS. We conclude that the Ang II-AT1R-PKC axis may directly influence nuclear function within the kidney through a redox sensitive pathway.
摘要
我们和其他研究人员已报道血管紧张素II 1型受体（AT1R）在肾细胞核上有显著表达；因此，本研究评估了分离细胞核内细胞内AT1R的功能途径和分布。血管紧张素II（1nM）刺激了DCF荧光，这是活性氧（ROS）的核内指标，而AT1R拮抗剂氯沙坦或NADPH氧化酶（NOX）抑制剂二苯基碘（DPI）消除了ROS的增加。用抗核孔蛋白62（Nup62）和AT1R或NADPH氧化酶亚型NOX4的抗体对细胞核进行双重标记，通过流式细胞术显示Nup62和AT1R完全重叠（99%），而NOX4存在于65%的细胞核上。用蛋白激酶C（PKC）激动剂处理细胞核会增加ROS，而PKC抑制剂GF109203X或磷脂酰肌醇-3激酶（PI3激酶）抑制剂LY294002消除了血管紧张素II对ROS的刺激。我们得出结论，血管紧张素II-AT1R-PKC轴可能通过氧化还原敏感途径直接影响肾脏内的核功能。
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