Neuroglobin is up-regulated by and protects neurons from hypoxic-ischemic injury
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Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved October 4, 2001 (received for review September 4, 2001)
Abstract
Globins are oxygen-binding heme proteins present in bacteria, protists, fungi, plants, and animals. Their functions have diverged widely in evolution, and include binding, transport, scavenging, detoxification, and sensing of gases like oxygen, nitric oxide, and carbon monoxide. Neuroglobin (Ngb) is a recently discovered monomeric globin with high affinity for oxygen and preferential localization to vertebrate brain. No function for Ngb is known, but its affinity for oxygen and its expression in cerebral neurons suggest a role in neuronal responses to hypoxia or ischemia. Here we report that Ngb expression is increased by neuronal hypoxia in vitro and focal cerebral ischemia in vivo, and that neuronal survival after hypoxia is reduced by inhibiting Ngb expression with an antisense oligodeoxynucleotide and enhanced by Ngb overexpression. Both induction of Ngb and its protective effect show specificity for hypoxia over other stressors. We conclude that hypoxia-inducible Ngb expression helps promote neuronal survival from hypoxic-ischemic insults.
Footnotes
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↵ * To whom reprint requests should be addressed. E-mail: dgreenberg{at}buckinstitute.org.
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This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
- DAPI,
- 4′,6-diamidino-2-phenylindole;
- HIF-1,
- hypoxia-inducible factor-1;
- MTT,
- 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide;
- NeuN,
- neuronal nuclear antigen;
- Ngb,
- neuroglobin;
- ODN,
- oligodeoxynucleotide;
- SNP,
- sodium nitroprusside;
- TBE,
- trypan blue exclusion
- Copyright © 2001, The National Academy of Sciences
