Hypoxia-inducible factor-1 and neuroglobin expression

Neuroglobin (Ngb) is a hypoxia-inducible protein with cytoprotective effects in animal models of stroke, Alzheimer's disease, and related disorders, but the molecular mechanisms involved in its induction are unknown. We tested the hypothesis that hypoxia-inducible factor-1 (HIF-1) regulates Ngb levels, using shRNA-mediated knockdown and lentiviral vector-mediated overexpression of the HIF-1α subunit, in cultured neural (HN33) cells. HIF-1α knockdown decreased and HIF-1α overexpression increased Ngb levels, consistent with a connection between HIF-1 and Ngb induction. These findings may have implications for understanding the hypoxia-response repertoire of neural cells and devising therapeutic strategies for neurologic disorders.

► Knockdown of hypoxia-inducible factor-1 α (HIF-1α) decreased neuroglobin (Ngb) levels in cultured mouse neural (HN33) cells.
► Forced overexpression of HIF-1α increased neuroglobin (Ngb) levels in the same cell line.
► Thus, induction of HIF-1α and of Ngb may be interrelated elements of the hypoxia-response repertoire in neural cells.