Hypoxia/ischemia and the regulation of neuroglobin and cytoglobin expression.

In analogy to hemoglobin (Hb) and myoglobin (Mb), neuroglobin (Ngb) and cytoglobin (Cygb) are supposed to be involved in oxygen (O2) storage and delivery. The Cygb gene harbours both conserved HREs and mRNA stabilization sites, strongly suggestive of an oxygen-dependent regulation. We examined the relative transcriptional changes of Ngb and Cygb in a situation of chronic hypoxia using real-time quantitative PCR. We could conclude that Cygb is a hypoxia-induced gene, which is transcriptionally upregulated during chronic hypoxia in a hippocampal neuronal cell line and in multiple murine metabolically active tissues. The mechanism of induction of Cygb is HIF-1alpha dependent. HIF-1 is unique among mammalian transcription factors with respect to the specificity and sensitivity of its induction by hypoxia. Ngb expression seems to be regulated using other response elements and is less influenced by hypoxia.