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Cytoglobin Is a Stress-responsive Hemoprotein Expressed in the Developing and Adult Brain

Pradeep P.A. Mammen, John M. Shelton, Qiu Ye, Shane B. Kanatous, Amanda J. McGrath, James A. Richardson and Daniel J. Garry

Departments of Internal Medicine (PPAM,JMS,QY,SBK,AJM,DJG), Pathology (JAR), Molecular Biology (JAR,DJG), and the Donald W. Reynolds Cardiovascular Clinical Research Center (PPAM,JMS,DJG), University of Texas Southwestern Medical Center, Dallas, Texas

Correspondence to: Daniel J. Garry, Department of Internal Medicine, NB 11.118A, 5323 Harry Hines Blvd., University of Texas Southwestern Medical Center, Dallas, TX 75390-8573. E-mail: daniel.garry{at}utsouthwestern.edu. Co-corresponding author: Pradeep P.A. Mammen. E-mail: pradeep.mammen{at}utsouthwestern.edu

Cytoglobin (Cygb) is a novel tissue hemoprotein relatively similar to myoglobin (Mb). Because Cygb shares several structural features with Mb, we hypothesized that Cygb functions in the modulation of oxygen and nitric oxide metabolism or in scavenging free radicals within a cell. In the present study we examined the spatial and temporal expression pattern of Cygb during murine embryogenesis. Using in situ hybridization, RT-PCR, and Northern blot analyses, limited Cygb expression was observed during embryogenesis compared with Mb expression. Cygb expression was primarily restricted to the central nervous system and neural crest derivatives during the latter stages of development. In the adult mouse, Cygb is expressed in distinct regions of the brain as compared with neuroglobin (Ngb), another globin protein, and these regions are responsive to oxidative stress (i.e., hippocampus, thalamus, and hypothalamus). In contrast to Ngb, Cygb expression in the brain is induced in response to chronic hypoxia (10% oxygen). These results support the hypothesis that Cygb is an oxygen-responsive tissue hemoglobin expressed in distinct regions of thenormoxic and hypoxic brain and may play a key role in the response of the brain to ahypoxic insult. (J Histochem Cytochem 54:1349–1361, 2006)

Key Words: embryogenesis • brain • hypoxia • myoglobin • neuroglobin • neurogenesis • oxidative stress

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