Cytoglobin Is a Stress-responsive Hemoprotein That Is Expressed in the Developing and Adult Brain
Pradeep P.A. Mammen 1, John M. Shelton 1, Qiu Ye 1, Shane B. Kanatous 1, Amanda J. McGrath 1, James A. Richardson 1 and Daniel J. Garry 1*
1 Departments of Internal Medicine (PPAM,JMS,QY,SBK,AJM,DJG), Pathology (JAR), and Molecular Biology (JAR,DJG) and the Donald W. Reynolds Cardiovascular Clinical Research Center (PPAM,JMS,DJG), University of Texas Southwestern Medical Center, Dallas, Texas
* To whom correspondence should be addressed. E-mail: daniel.garry{at}utsouthwestern.edu .
Submitted on May 4, 2006
Accepted on 21 July 2006
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Abstract |
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Cytoglobin is a novel tissue hemoprotein that is relatively similar to myoglobin. Since cytoglobin shares several structural features with myoglobin, we hypothesized that cytoglobin 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 cytoglobin during murine embryogenesis. Using in situ hybridization, RT-PCR, and northern blot analyses, limited cytoglobin expression was observed during embryogenesis compared with myoglobin expression. Cytoglobin expression was primarily restricted to the central nervous system and neural crest derivatives during the latter stages of development. In the adult mouse, cytoglobin is expressed in distinct regions of the brain as compared with neuroglobin, another globin protein, and these regions are responsive to oxidative stress (i.e., hippocampus, thalamus, and hypothalamus). In contrast to neuroglobin, cytoglobin expression in the brain is induced in response to chronic hypoxia (10% oxygen). These results support the hypothesis that cytoglobin is an oxygen responsive tissue hemoglobin that is expressed in distinct regions of the normoxic and hypoxic brain and may play a key role in the response of the brain to a hypoxic insult.
Key Words:
embryogenesis, brain, hypoxia, myoglobin, neuroglobin, neurogenesis, oxidative stress