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Status |
Public on Mar 16, 2006 |
Title |
Hypoxia responsive genes in human Burkitt’s lymphoma cell line, P493-6. |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Activation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia. We found that HIF-1 also actively suppresses glucose metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA. Forced PDK1 expression in hypoxic HIF-1α-null cells increases ATP levels, attenuates hypoxic ROS generation and rescues these cells from hypoxia-induced apoptosis. These studies reveal a novel hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production. Keywords: Hypoxia responsive, case control
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Overall design |
We sought to determine by microarray analysis of gene expression the genes responsive to hypoxia using the human B lymphocyte cell line, P493-6. Hypoxia-responsive genes were globally assessed in cells incubated in 0.1% O2 for 29 hours at which the highest HIF-1 levels were obtained
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Contributor(s) |
Kim J, Tchernyshyov I, Semenza GL, Dang CV |
Citation(s) |
16517405 |
Submission date |
Jan 23, 2006 |
Last update date |
Mar 25, 2019 |
Contact name |
Chi V. Dang |
E-mail(s) |
cvdang@jhmi.edu
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Phone |
410-955-2773
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Fax |
410-955-0185
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Organization name |
Johns Hopkins University, School of Medicine
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Department |
Medicine
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Street address |
720 Rutland Ave, Ross 1032
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City |
Baltimore |
State/province |
MD |
ZIP/Postal code |
21210 |
Country |
USA |
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Platforms (1) |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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Samples (4)
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Relations |
BioProject |
PRJNA95239 |