Regulation and role of neuroglobin and cytoglobin under hypoxia.

Neuroglobin (Ngb) and cytoglobin (Cygb) are two novel members of the globin superfamily that are ubiquitously present in vertebrates. Their exact physiological roles are still uncertain. Here we review the expression of Ngb and Cygb, with particular emphasis on their regulation and potential role under hypoxia. Ngb expression is confined to neurons and some endocrine tissues. At the subcellular level, Ngb is associated with the presence of mitochondria and thus linked to the oxidative metabolism. Hypoxia or ischemic insults most likely do not strongly increase Ngb levels in the rodent brain. This might be explained by the fact that most mammals are not adapted to low oxygen levels. In zebrafish and turtle, however, which live in an environment with naturally changing oxygen conditions, hypoxia dramatically increases Ngb expression in the brains. We also found that hypoxia-tolerant species (e.g. the mole rat Spalax and goldfish) express more Ngb in their brains than their oxygen-deprivation sensitive relatives. These data suggest that Ngb may have a myoglobin-like role and supplies oxygen to the respiratory chain of the metabolically highly active neurons, or protect them from reactive oxygen species. Cygb is predominantly expressed in fibroblasts and related cell types, but also in distinct nerve cell populations. Cygb levels are significantly elevated at low oxygen levels in the fibroblast cell lineage. Cell culture data suggest that in fibroblasts Cygb is involved in cell proliferation, possibly in collagen synthesis. In neurons, there is evidence for an additional role of Cygb related to nitric oxide metabolism.