Mammalian gene expression in hypoxic conditions 1 1 Presented at the 94th Annual Meeting of the Deutsche Zoologische Gesellschaft in Osnabrück, June 4–8, 2001

Hypoxia induces gene expression of specific genes such as erythropoietin (Epo) and vascular endothelial growth factor (VEGF) that allow physiological adaptation to the environmental conditions at the cellular, local, and systemic levels. Reduced oxygenation is also a common precursor of many pathological processes, including coronary artery defects, ischemia, and malignant tumour formation. The hypoxia-inducible transcription factor HIF-1, a heterodimer consisting of the oxygen-regulated α-subunit and the constitutively expressed β or ARNT-subunit, serves as a master regulator of oxygen-dependent gene expression. We observed that upon hypoxic exposure of HeLa cells in tonometer, accumulation of HIF-1α occurred within two minutes, while reoxygenation strongly reduced HIF-1α levels within four to eight minutes. Thus, hypoxia leads to a rapid cellular adaptation. In another line of investigation, we analysed the impact of hypoxia-independent overexpression of Epo in transgenic mice. Despite a hematocrit of about 80% the transgenic mice did not develop hypertension or thromboembolic complications.