Hypoxia up-regulates triosephosphate isomerase expression via a HIF-dependent pathway.
The glycolytic enzyme triosephosphate isomerase (TPI) catalyses the reversible conversion of dihydroxyacetone phosphate into glyceraldehyde-3-phosphate. We report here that the expression of TPI at both the mRNA and protein levels is increased by hypoxia in vivo and in vitro. The temporal pattern of hypoxic TPI induction is very similar to that of genes triggered by the hypoxia-inducible transcription factor (HIF) and is mimicked characteristically by cobalt and by deferoxamine, but is absent in cells with a defective aryl hydrocarbon receptor nuclear translocator (ARNT, here HIF-1beta) and in cells lacking HIF-1alpha protein. We conclude from these findings that the expression of TPI is regulated via the HIF pathway and thus belongs to the family of classic oxygen-regulated genes. The physiological meaning of an increased expression of TPI in hypoxygenated tissues is probably to increase the flow of triosephosphates through the glycolytic cascade thus leading to an increase of anaerobic energy generation.
Gess
Bernhard
B
Institut für Physiologie der Universität Regensburg, 93040, Regensburg, Germany.
Hofbauer
Karl-Heinz
KH
Deutzmann
R
R
Kurtz
Armin
A
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology; D009687:Nuclear Proteins / Q000502:physiology*; D023282:Nuclease Protection Assays; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014305:Triose-Phosphate Isomerase / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D000199:Actins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497444:Hif1a protein, rat; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D002248:Carbon Monoxide; D014305:Triose-Phosphate Isomerase