title: Mitochondrial ROS-K+ channel signaling pathway regulated secretion of human pulmonary artery endothelial cells.
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.
authors.affiliation: Department of Respiratory Medicine , The First Affiliated Hospital of Wenzhou Medical College, China. ouyangjsh@yahoo.com.cn
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: Ouyang
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Li
authors.forename: Cheng-Ye
authors.initials: CY
authors.lastname: Li
authors.forename: Chang
authors.initials: C
authors.lastname: Cai
authors.forename: Cheng-Shui
authors.initials: CS
authors.lastname: Chen
authors.forename: Shao-Xian
authors.initials: SX
authors.lastname: Chen
authors.forename: Yan-Fan
authors.initials: YF
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Xie
mesh_terms: D000171:Acrolein / Q000494:pharmacology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051666:Kv1.5 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012402:Rotenone / Q000494:pharmacology; D015398:Signal Transduction; D014475:Uncoupling Agents / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D051666:Kv1.5 Potassium Channel; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D012402:Rotenone; D000171:Acrolein; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D002118:Calcium