Adenosine A2A receptors regulate oxidative stress formation in rat pheochromocytoma PC12 cells during serum deprivation

Activation of A(2A) adenosine receptors (A(2A)-Rs) was found to prevent reactive oxygen species (ROS) formation and apoptosis in serum-deprived pheochromocytoma PC12 cells. A protein kinase A (PKA) inhibitor not only blocked the anti-apoptotic roles of A(2A)-R but also reversed A(2A)-R-induced suppression of ROS formation, indicating a PKA-dependent pathway in preventing ROS formation and apoptosis. PKA stimulators and antioxidants prevented serum-deprived ROS formation and apoptosis. In addition, A(2A)-R activation also prevented H2O2-induced cell death, further suggesting the protective roles of A(2A)-R in antagonizing oxidative stress and cell death. Finally, antioxidative system-interrupting agents attenuated A(2A)-R-mediated protection. Taken together, these data indicate that PKA-dependent regulation and attenuation of oxidative stress by A(2A)-R may play at least some roles in preventing serum-deprived PC12 cell apoptosis. (C) 2003 Elsevier Ireland Ltd. All rights reserved.