Membrane depolarization and NADPH oxidase activation in aortic endothelium during ischemia reflect altered mechanotransduction
| Autor: | Yefim Manevich, Aron B. Fisher, Qunwei Zhang, Shampa Chatterjee, Ikuo Matsuzaki, Kris DeBolt |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
Endothelium Physiology Ischemia Mechanotransduction Cellular Membrane Potentials Rats Sprague-Dawley Mice Physiology (medical) medicine Animals Mechanotransduction Potassium Channels Inwardly Rectifying Aorta Cells Cultured chemistry.chemical_classification Membrane potential Mice Knockout Reactive oxygen species Oxidase test NADPH oxidase biology Cell Membrane Cytochromes c Endothelial Cells NADPH Oxidases Depolarization medicine.disease Rats Enzyme Activation medicine.anatomical_structure Biochemistry chemistry cardiovascular system biology.protein Biophysics Endothelium Vascular Stress Mechanical Cardiology and Cardiovascular Medicine Reactive Oxygen Species |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 288(1) |
| ISSN: | 0363-6135 |
| Popis: | We previously showed that “ischemia” (abrupt cessation of flow) leads to rapid membrane depolarization and increased generation of reactive oxygen species (ROS) in lung microvascular endothelial cells. This response is not associated with anoxia but, rather, reflects loss of normal shear stress. This study evaluated whether a similar response occurs in aortic endothelium. Plasma membrane potential and production of ROS were determined by fluorescence microscopy and cytochrome c reduction in flow-adapted rat or mouse aorta or monolayer cultures of rat aortic endothelial cells. Within 30 s after flow cessation, endothelial cells that had been flow adapted showed plasma membrane depolarization that was inhibited by pretreatment with cromakalim, an ATP-sensitive K+(KATP) channel agonist. Flow cessation also led to ROS generation, which was inhibited by cromakalim and the flavoprotein inhibitor diphenyleneiodonium. Aortic endothelium from mice with “knockout” of the KATPchannel (KIR6.2) showed a markedly attenuated change in membrane potential and ROS generation with flow cessation. In aortic endothelium from mice with knockout of NADPH oxidase (gp91phox), membrane depolarization was similar to that in wild-type mice but ROS generation was absent. Thus rat and mouse aortic endothelial cells respond to abrupt flow cessation by KATPchannel-mediated membrane depolarization followed by NADPH oxidase-mediated ROS generation, possibly representing a cell-signaling response to altered mechanotransduction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|