Lung endothelial cell proliferation with decreased shear stress is mediated by reactive oxygen species
| Autor: | Aron B. Fisher, Shampa Chatterjee, Muniswamy Madesh, Yefim Manevich, Tatyana N. Milovanova, Kris DeBolt, Irina Kotelnikova, Jonni S. Moore |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pulmonary Circulation
Cell signaling Physiology Ischemia Apoptosis Mice Glyburide medicine Animals Hypoglycemic Agents Vasoconstrictor Agents Potassium Channels Inwardly Rectifying Mechanotransduction Lung chemistry.chemical_classification Reactive oxygen species Membrane Glycoproteins NADPH oxidase biology Angiotensin II Endothelial Cells NADPH Oxidases Depolarization Cell Biology medicine.disease Mice Mutant Strains Potassium channel Cell biology Mice Inbred C57BL Endothelial stem cell Oxidative Stress Phenotype chemistry Pulsatile Flow NADPH Oxidase 2 biology.protein Stress Mechanical Reactive Oxygen Species Cell Division Signal Transduction |
| Zdroj: | American Journal of Physiology-Cell Physiology. 290:C66-C76 |
| ISSN: | 1522-1563 0363-6143 |
| Popis: | Acute cessation of flow (ischemia) leads to depolarization of the endothelial cell (EC) membrane mediated by KATP channels and followed by production of reactive oxygen species (ROS) from NADPH oxidase. We postulated that ROS are a signal for initiating EC proliferation associated with the loss of shear stress. Flow cytometry was used to identify proliferating CD31-positive pulmonary microvascular endothelial cells (mPMVECs) from wild-type, Kir6.2−/−, and gp91 phox−/− mice. mPMVECs were labeled with PKH26 and cultured in artificial capillaries for 72 h at 5 dyn/cm2 (flow adaptation), followed by 24 h of stop flow or continued flow. ROS production during the first hour of ischemia was markedly diminished compared with wild-type mice in both types of gene-targeted mPMVECs. Cell proliferation was defined as the proliferation index (PI). After 72 h of flow, >98% of PKH26-labeled wild-type mPMVECs were at a single peak (PI 1.0) and the proportion of cells in the S+G2/M phases were at 5.8% on the basis of cell cycle analysis. With ischemia (24 h), PI increased to 2.5 and the ratio of cells in S+G2/M phases were at 35%. Catalase, diphenyleneiodonium, and cromakalim markedly inhibited ROS production and cell proliferation in flow-adapted wild-type mPMVECs. Significant effects of ischemia were not observed in Kir6.2−/− and gp91 phox−/− cells. ANG II activation of NADPH oxidase was unaffected by KATP gene deletion. Thus loss of shear stress in flow-adapted mPMVECs results in cell division associated with ROS generated by NADPH oxidase. This effect requires a functioning cell membrane KATP channel. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|