Abstract

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 H 2O 2-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.

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