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 the mouse, 82% to the rat, human, dog, and sheep, and 69% to the chicken GLUT 3 peptides. Using Northern blot analysis, we investigated the tissue and brain cellular distribution of GLUT 1 and GLUT 3 expression. In addition, we 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, GLUT 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. Both GLUT 1 and GLUT 3 mRNA levels demonstrated a similar developmental progression (p<0.05) secondary to post-transcriptional mechanisms. Further, while hypoxic-ischemia did not significantly affect brain GLUT 1 mRNA and protein, it altered GLUT 3 mRNA levels in a region-specific manner, with a three-fold increase in the cerebral cortex, a two-fold increase in the hippocampus, and a 50% increase in the caudate nucleus (p<0.05). We conclude, that the rabbit GLUT 3 peptide sequence exhibits 82-84% homology to that of other species in the coding region with a 62-89% sequence identity in the 3'-untranslated region. The tissue-specific expression of rabbit GLUT 3 mimics that of the human closely. Postnatal development and hypoxic-ischemia with reperfusion injury cause an increase in brain GLUT 3 expression, as a response to synaptogenesis and substrate deprivation, respectively.
Devaskar
S U
SU
Division of Neonatology and Developmental Biology, Department of Pediatrics, 300 Halket Street, University of Pittsburgh, Magee-Womens Research Institute, Pittsburgh, PA, 15213-3180, USA. sdevaskar@mail.magee.edu
Rajakumar
P A
PA
Mink
R B
RB
McKnight
R A
RA
Thamotharan
S
S
Hicks
S J
SJ
D000375:Aging / Q000378:metabolism; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D001483:Base Sequence / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000502:physiology; D005333:Fetus / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D000860:Hypoxia / Q000378:metabolism*; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger