Neuroprotective function of human neuroglobin is correlated with its guanine nucleotide dissociation inhibitor activity.
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.
Watanabe
Seiji
S
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
Wakasugi
Keisuke
K
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology; D005914:Globins / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000078787:Neuroglobin; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D013223:Statistics as Topic
D020730:Guanine Nucleotide Dissociation Inhibitors; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D005914:Globins