Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation
| Autor: | Elise A. Hopkins, Emran Sheikh, Kirsten Bass Wilkins, Gregory B. Bulkley, Manabu Takano, Avedis Meneshian, Yasuhiko Yamakawa |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Umbilical Veins
Xanthine Oxidase P-selectin Physiology Biology Hemostatics chemistry.chemical_compound Downregulation and upregulation Physiology (medical) Humans Xanthine oxidase Cells Cultured Homeodomain Proteins chemistry.chemical_classification Reactive oxygen species Oxidase test NADPH oxidase Dose-Response Relationship Drug Thrombin NADPH Oxidases Nuclear Proteins Up-Regulation Cell biology Endothelial stem cell P-Selectin chemistry Biochemistry Antennapedia Homeodomain Protein biology.protein Endothelium Vascular Signal transduction Reactive Oxygen Species Cardiology and Cardiovascular Medicine Signal Transduction Transcription Factors |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 283:H2054-H2061 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | Endothelial cell ICAM-1 upregulation in response to TNF-α is mediated in part by reactive oxygen species (ROS) generated by the endothelial membrane-associated NADPH oxidase and occurs maximally after 4 h as the synthesis of new protein is required. However, thrombin-stimulated P-selectin upregulation is bimodal, the first peak occurring within minutes. We hypothesize that this early peak, which results from the release of preformed P-selectin from within Weibel-Palade bodies, is mediated in part by ROS generated from the endothelial membrane-associated xanthine oxidase. We found that this rapid expression of P-selectin on the surface of endothelial cells was accompanied by qualitatively parallel increases in ROS generation. Both P-selectin expression and ROS generation were inhibited, dose dependently, by the exogenous administration of disparate cell-permeable antioxidants and also by the inhibition of either of the known membrane-associated ROS-generating enzymes NADPH oxidase or xanthine oxidase. This rapid, posttranslational cell signaling response, mediated by ROS generated not only by the classical NADPH oxidase but also by xanthine oxidase, may well represent an important physiological trigger of the microvascular inflammatory response. |
| Databáze: | OpenAIRE |
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