Continuous, but not Episodic Hypoxia, Induces Creb Phosphorylation in Rat Carotid Body Type I Cells

The CB sensitivity to hypoxia is increased following sustained, long-term hypoxia such as in ventilatory acclimatization to high altitude (Bisgard 1994). The mechanisms underlying the cellular responses and adaptation to hypoxia are poorly understood. It is assumed that a major component of this adaptation is regulation of gene expression. cAMP response element-binding protein (CREB) is a nuclear protein. CREB is activated upon phosphorylation at Ser and modulates the transcription of genes with cAMP response elements (CRE) in their promoters (Ginty 1997). Recently, it has been shown that hypoxia induces phosphorylation of CREB at Ser in cultured PC 12 cells (Beitner-Johnson and Millhorn 1998), which are similar to the CB type I cells in several important characteristics related to oxygen-dependent gene regulation.