Hypoxia-induced hypomyelination in the developing brain is mammalian target of rapamycin-4E-binding protein-1 signaling dependent.
We hypothesized that changes in the expression levels of genes in the mammalian target of rapamycin are involved in the hypoxia-induced growth retardation in the brain including hypomyelination. Microarray and proteomic studies showed a 2.3-fold increase in the expression levels of eukaryotic translation initiation factor 4E-binding protein-1 and a 3-fold decrease in the levels of FK506-binding protein-1 in a neonatal model of hypoxia, indicating a signal transduction impairment through mammalian target of rapamycin (mTOR). Analysis of hypoxic brain showed a marked decrease in the phosphorylation levels of 4E-binding protein-1, suggesting a reduction of mTOR activity. These data suggest that suppression of mTOR may be the mechanism underlying hypoxia-induced hypomyelination observed in the developing brain.
Bilali
Faton
F
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York 10595, USA.
Kumar
Pranav
P
Feerick
John
J
Berezin
Stuart
S
Farahani
Reza
R
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D039642:Eukaryotic Initiation Factors; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D051379:Mice; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000378:metabolism*; D040081:Protein Array Analysis; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins