Neuroglobin protects neurons against oxidative stress in global ischemia.
Neuroglobin (Ngb) is a recently discovered globin that affords protection against hypoxic/ischemic-induced cell injury in brain. Hypoxic/ischemic injury is associated with accumulation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS). In previous studies, we found that Ngb has antioxidative properties, and protects PC-12 cells against hypoxia- and β-amyloid-induced cell death. To further delineate the potential role of Ngb in protection against cerebral ischemia-reperfusion injury in vivo, we developed a transgenic mouse line that overexpresses Ngb. Hippocampal ischemia-reperfusion injury was induced by a 10-minute bilateral occlusion of the common carotid arteries, and the animal brains were assessed 3 days later. CA1 neural injury was determined by cresyl violet staining. Lipid peroxidation was assessed using a malonyldialdehyde assay kit, whereas ROS/RNS accumulation was determined by Het staining in the CA1 hippocampal region. Hippocampal Ngb mRNA and protein expressions were assessed by reverse transcriptase-PCR and western blotting, respectively. Neuroglobin was successfully overexpressed in the hippocampus of Ngb transgenic mice. After ischemia-reperfusion, CA1 ROS/RNS production and lipid peroxidation were markedly decreased in Ngb transgenic mice compared with wild-type mice. Furthermore, CA1 neuronal injury was also markedly reduced. Thus, Ngb may confer protection against ischemia-reperfusion injury in the brain through its intrinsic antioxidant properties.
Li
Richard Changxun
RC
Department of Pediatrics, University of Chicago, Chicago, Illinois, USA.
Guo
Shang Zhi
SZ
Lee
Seung Kwan
SK
Gozal
David
D
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D015854:Up-Regulation
D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D005914:Globins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase