The role of protein kinase A in hypoxia-induced PC-12 cell death.

Abstract

Hypoxia is characterized by an inadequate oxygen supply to the tissues in proportion to their metabolic needs, and is a primary factor in traumatic CNS injury, strokes, cardiopulmonary diseases, and obstructive sleep apnea. The cAMP-dependent protein kinase (PKA) has been attributed a role as an antiapoptotic kinase as well as a pro-apoptotic signal. Thus the role of PKA in hypoxia-induced cell survival is currently unclear. Antioxidant treatment blocked hypoxia-induced cell death, but was not sufficient to prevent depletion of ATP or to modulate the metabolic pathways.Thus, this finding indicates that hypoxia-induced metabolic regulation and energy depletion occur independently of oxidative stress.Consequently, the PKA signaling pathway appears to contribute to hypoxia-induced cell death through its regulatory effects on oxidative stress and metabolic pathways. Modulation of the PKA signaling pathway could provide novel therapeutic strategies to improve cellular adaptation and recovery in the many pathologies characterized by periods of hypoxia.