|
| 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
|
| 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
|
| |
|
| 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
|
| |
|
| 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
|
| Phone |
410-955-2773
|
| Fax |
410-955-0185
|
| Organization name |
Johns Hopkins University, School of Medicine
|
| Department |
Medicine
|
| Street address |
720 Rutland Ave, Ross 1032
|
| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21210 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA95239 |
Less...
More...