Effect of development and hypoxic-ischemia upon rabbit brain glucose transporter expression

We have cloned and sequenced a full length rabbit GLUT 1 and partial rabbit GLUT 3 cDNAs. The derived rabbit GLUT 3 peptide revealed 84% homology to t he mouse, 82% to the rat, human, dog, and sheep, and 69% to the chicken GLU T 3 peptides. Using Northern blot analysis, we investigated the tissue and brain cellular distribution of GLUT 1 and GLUT 3 expression. In addition, w e examined the effect of development and hypoxic-ischemia upon brain GLUT 1 and GLUT 3 mRNA levels. While GLUT 1 mRNA was observed in most tissues, GL UT 3 was expressed predominantly in the brain, placenta, stomach, and lung with minor amounts in the heart, kidney and skeletal muscle. In the brain, both GLUT 1 and GLUT 3 were noted in neuron- and glial-enriched cultures. B oth GLUT 1 and GLUT 3 mRNA levels demonstrated a similar developmental prog ression(p < 0.05) secondary to post-transcriptional mechanisms. Further, wh ile hypoxic-ischemia did not significantly affect brain GLUT 1 mRNA and pro tein, it altered GLUT 3 mRNA levels in a region-specific manner, with a thr ee-fold increase in the cerebral cortex, a two-fold increase in the hippoca mpus, and a 50% increase in the caudate nucleus (p < 0.05). We conclude, th at the rabbit GLUT 3 peptide sequence exhibits 82-84% homology to that of o ther species in the coding region with a 62-89% sequence identity in the 3' -untranslated region. The tissue-specific expression of rabbit GLUT 3 mimic ks that of the human closely. Postnatal development and hypoxic-ischemia wi th reperfusion injury cause an increase in brain GLUT 3 expression, as a re sponse to synaptogenesis and substrate deprivation, respectively. (C) 1999 Elsevier Science B.V. All rights reserved.