PUBLICATION
Neuroprotective function of human neuroglobin is correlated with its guanine nucleotide dissociation inhibitor activity
- Authors
- Watanabe, S., and Wakasugi, K.
- ID
- ZDB-PUB-080306-27
- Date
- 2008
- Source
- Biochemical and Biophysical Research Communications 369(2): 695-700 (Journal)
- Registered Authors
- Wakasugi, Keisuke
- Keywords
- Globin, Oxidative stress, GDI, Neuroprotective mechanism, PC12
- MeSH Terms
-
- Animals
- Apoptosis/physiology*
- Cell Hypoxia/physiology
- Globins/metabolism*
- Guanine Nucleotide Dissociation Inhibitors/metabolism*
- Humans
- Nerve Tissue Proteins/metabolism*
- Neurons/cytology*
- Neurons/metabolism*
- Neuroprotective Agents/metabolism*
- Oxidative Stress/physiology*
- PC12 Cells
- Rats
- Statistics as Topic
- PubMed
- 18302932 Full text @ Biochem. Biophys. Res. Commun.
Citation
Watanabe, S., and Wakasugi, K. (2008) Neuroprotective function of human neuroglobin is correlated with its guanine nucleotide dissociation inhibitor activity. Biochemical and Biophysical Research Communications. 369(2):695-700.
Abstract
Mammalian neuroglobin (Ngb) is involved in neuroprotection under oxidative stress conditions such as ischemia and reperfusion. However, the neuroprotective mechanism remains unclear. We previously demonstrated that human ferric Ngb binds to the alpha-subunits of heterotrimeric G proteins (Galpha(i/o)) and acts as a guanine nucleotide dissociation inhibitor (GDI) for Galpha(i/o). In the present study, we used a protein delivery reagent, Chariot, to investigate whether the GDI activity of human Ngb plays an important role in its neuroprotective activity under oxidative stress conditions. We showed that human Ngb mutants, which retained GDI activities, rescued pheochromocytoma PC12 cell death caused by hypoxia/reoxygenation as did human wild-type Ngb. In contrast, zebrafish Ngb and human Ngb mutants, which did not function as GDI proteins, did not rescue cell death. These results clearly show that the GDI activity of human Ngb is tightly correlated with its neuroprotective activity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping