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Division of Neonatology and Developmental Biology, Department of Pediatrics, University of Pittsburgh, Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213-3180
We examined the molecular mechanisms that
mediate the developmental increase in murine whole brain 2-deoxyglucose
uptake. Northern and Western blot analyses revealed an age-dependent
increase in brain GLUT-1 (endothelial cell and glial) and GLUT-3
(neuronal) membrane-spanning facilitative glucose transporter mRNA and
protein concentrations. Nuclear run-on experiments revealed that these developmental changes in GLUT-1 and -3 were regulated
posttranscriptionally. In contrast, the mRNA and protein levels of the
mitochondrially bound glucose phosphorylating hexokinase I enzyme were
unaltered. However, hexokinase I enzyme activity increased in an
age-dependent manner suggestive of a posttranslational modification
that is necessary for enzymatic activation. Together, the postnatal
increase in GLUT-1 and -3 concentrations and hexokinase I enzymatic
activity led to a parallel increase in murine brain 2-deoxyglucose
uptake. Whereas the molecular mechanisms regulating the
increase in the three different gene products may vary, the
age-dependent increase of all three constituents appears essential for
meeting the increasing demand of the maturing brain to fuel the
processes of cellular growth, differentiation, and neurotransmission.
glucose transporters; hexokinase; neurons; endothelial cells; glial cells
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