Adenosine A2A receptor signaling regulation of cardiac NADPH oxidase activity
| Autor: | Catherine Ledent, Martin Hussey, Susanna M.O. Hourani, Ian Kitchen, David Ribé, David Sawbridge, Sapna Thakur, Jian-Mei Li |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Adenosine Time Factors Receptor Adenosine A2A MAP Kinase Signaling System Adenosine A2A receptor Biology Models Biological Biochemistry Gene Expression Regulation Enzymologic Article Mice Physiology (medical) Internal medicine medicine Animals Myocyte Phosphorylation Receptor Mice Knockout chemistry.chemical_classification Reactive oxygen species NADPH oxidase Myocardium NADPH Oxidases Molecular biology Endocrinology Microscopy Fluorescence chemistry biology.protein Signal transduction Reactive Oxygen Species Signal Transduction medicine.drug |
| Zdroj: | Free Radical Biology and Medicine. 44:1433-1442 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2007.12.035 |
| Popis: | Cardiac tissues express constitutively an NADPH oxidase, which generates reactive oxygen species (ROS) and is involved in redox signaling. Myocardial metabolism generates abundant adenosine, which binds to its receptors and plays important roles in cardiac function. The adenosine A2A receptor (A2AR) has been found to be expressed in cardiac myocytes and coronary endothelial cells. However, the role of the A2AR in the regulation of cardiac ROS production remains unknown. We found that knockout of A2AR significantly decreased (39+/-8%) NADPH-dependent O2- production in mouse hearts compared to age (10 weeks)-matched wild-type controls. This was accompanied by a significant decrease in Nox2 (a catalytic subunit of NADPH oxidase) protein expression, and down-regulation of ERK1/2, p38MAPK, and JNK phosphorylation (all P0.05). In wild-type mice, intraperitoneal injection of the selective A2AR antagonist SCH58261 (3-10 mg/kg body weight for 90 min) inhibited phosphorylation of p47phox (a regulatory subunit of Nox2), which was accompanied by a down-regulated cardiac ROS production (48+/-8%), and decreased JNK and ERK1/2 activation by 54+/-28% (all P0.05). In conclusion, A2AR through MAPK signaling regulates p47phox phosphorylation and cardiac ROS production by NADPH oxidase. Modulation of A2AR activity may have potential therapeutic applications in controlling ROS production by NADPH oxidase in the heart. |
| Databáze: | OpenAIRE |
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