News & Events

When

Date - March 13, 2020
1:00 pm - 2:00 pm

What

Professor and Associate Dean for Research
Department of Pharmaceutical Sciences
College of Pharmacy, Mercer University
Talk Title: The β2-adrenergic receptor-ROS axis: can a friend become a foe?

Abstract:

β2-Adrenergic receptor (β2AR) agonists are clinically used to elicit rapid bronchodilation for the treatment of bronchospasms in pulmonary diseases such as asthma and COPD, both of which exhibit characteristically high levels of reactive oxygen species (ROS); likely secondary to over-expression of ROS generating enzymes and chronically heightened inflammation. However, clinical use of β2AR agonists for pulmonary diseases often results in tolerance, or tachyphylaxis, to the bronchodilatory effect, the mechanisms of which are poorly understood.  Interestingly, β2AR has long-been linked to ROS, yet the involvement of ROS in β2AR function has not been as vigorously studied as other aspects of β2AR signaling. Indeed, a growing body of evidence links β2AR activation to intracellular ROS generation and importantly, also suggests that ROS play a role in regulating β2AR function. Our own studies demonstrate that ROS are generated upon β2AR agonism and that ROS uphold β2AR function by oxidizing cysteine residues via transient cysteine-S-sulfenation. The reciprocal interplay of the β2AR and ROS appear to endow this receptor with the ability to self-regulate ligand binding and signaling, yet, if this redox-axis is unfavorably altered as in pathological states such as asthma, β2AR function may be compromised.  We hypothesize this axis may play a role in β2AR agonist tachyphylaxis and our work, funded by NHLBI, seeks to characterize the involvement of ROS in regulation of β2AR functional responses.