beta2- but not beta1-adrenoceptor activation modulates intracellular oxygen availability.
beta-Adrenoceptors (beta-ARs) play a critical role in the regulation of cardiovascular function. Intracellular oxygen homeostasis is crucial for the survival of cardiomyocytes. However, it is still unclear whether beta-AR activation can modulate intracellular oxygen. Here we used mitochondrial and cytosolic target Renilla luciferase to detect intracellular oxygen concentration. Pharmacological experiments revealed that beta2-AR activation specifically regulates intracellular oxygen in cardiomyocytes and COS7 cells. This effect was abrogated by inhibitory G protein (Gi) inhibition, endothelial nitric oxide synthase (eNOS) blockade, and NO scavenging, implicating that the beta2-AR-Gi-eNOS pathway is involved in this regulation. beta2-AR activation increased the AMP/ATP ratio, AMPK activity, ROS production and prolyl hydroxylase activity. These effects also contribute to the regulation of beta2-AR signalling, thus providing an additional layer of complexity to enforce the specificity of beta1-AR and beta2-AR signalling. Collectively, the study provides novel insight into the modulation of oxygen homeostasis, broadens the scope of beta2-AR function, and may have crucial implications for beta2-AR signalling regulation.
Li
Jun
J
Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China.
Yan
Biao
B
Huo
Zhaoxia
Z
Liu
Ying
Y
Xu
Jiahong
J
Sun
Yunfu
Y
Liu
Yi
Y
Liang
Dandan
D
Peng
Luying
L
Zhang
Youyi
Y
Zhou
Zhao-Nian
ZN
Shi
Jingyi
J
Cui
Jianmin
J
Chen
Yi-Han
YH
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006706:Homeostasis; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D008929:Mitochondria, Heart / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
C547789:Adrb1 protein, rat; D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D009569:Nitric Oxide; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D049410:Luciferases, Renilla; D011393:Procollagen-Proline Dioxygenase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D055372:AMP-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D010100:Oxygen