1. Mitochondrial ROS-K+ channel signaling pathway regulated secretion of human pulmonary artery endothelial cells.
- Author
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Ouyang JS, Li YP, Li CY, Cai C, Chen CS, Chen SX, Chen YF, Yang L, and Xie YP
- Subjects
- Acrolein pharmacology, Blotting, Western, Calcium metabolism, Cell Proliferation drug effects, Cells, Cultured, Endothelin-1 genetics, Endothelin-1 metabolism, Endothelium, Vascular cytology, Endothelium, Vascular drug effects, Enzyme-Linked Immunosorbent Assay, Humans, Hydrogen Peroxide metabolism, Kv1.5 Potassium Channel genetics, Membrane Potential, Mitochondrial drug effects, Mitochondria drug effects, Nitric Oxide Synthase genetics, Nitric Oxide Synthase metabolism, Oxidative Stress drug effects, Pulmonary Artery cytology, Pulmonary Artery drug effects, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Rotenone pharmacology, Uncoupling Agents pharmacology, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Endothelium, Vascular metabolism, Kv1.5 Potassium Channel metabolism, Mitochondria metabolism, Pulmonary Artery metabolism, Reactive Oxygen Species metabolism, Signal Transduction
- Abstract
The objective was to investigate the molecular mechanism of mitochondrial reactive oxygen species (ROS) signaling regulation of pulmonary artery endothelial cell (HPAEC) secretion in the condition of oxidative stress. Acrolein (40 μM) induced HPAEC mitochondrial generation of ROS, rotenone (2 μmol/L) blocked mitochondrial respiratory chain complex I, cesium chloride (CsCl, 40 mmol/L)blocked K(+)channels, and saline (0.9 g/dl) were used as control. The generations of NOS, ET-1 and VEGF were determined with ELISA in the condition of different treatment reagents namely acrolein, acrolein plus rotenone, acrolein plus CsCl and saline. In the different reagent treatment of HPAECs, acrolein increased mitochondrial ROS, membrane potential, Kv1.5 mRNA and protein expression, intracellular calcium and the generation of NOS (determining NO production), ET-1 and VEGF, and those were reduced by rotenone. CsCl decreased the increment of membrane potential, the elevation of intracellular calcium and the upregulation of NOS, E-1 and VEGF expressions, which were induced by acrolein. The present study demonstrated that mitochondrial ROS-K(+)channel regulated HPAEC secretion of NO, ET-1 and VEGF in the condition of oxidative stress. Kv1.5 channel may be an important component of ROS-K+ channel signaling pathway, and intracellular calcium contributed to mitochondrial ROS-K(+) channel signaling modulation of HPAEC secretion.
- Published
- 2012
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