Compound C inhibits hypoxic activation of HIF-1 independent of AMPK.
The key transcription factor that regulates the cellular responses to hypoxia is hypoxia inducible factor-1 (HIF-1). The signaling mechanisms that regulate the hypoxic activation of HIF-1 are not fully understood. Our objective here was to test whether AMP-activated kinase (AMPK) was an upstream regulator of HIF-1. Our results show that AMPK is not required for the hypoxic activation of HIF-1. Interestingly, the AMPK inhibitor, Compound C, inhibits the hypoxic activation of HIF-1 independent of AMPK. Furthermore, we demonstrate that Compound C functions as a repressor of HIF-1 by inhibiting respiration and suppressing mitochondrial generated ROS.
Emerling
Brooke M
BM
Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA. bemerlin@bidmc.harvard.edu
Viollet
Benoit
B
Tormos
Kathryn V
KV
Chandel
Navdeep S
NS
D055372:AMP-Activated Protein Kinases; D015687:Cell Hypoxia; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D009097:Multienzyme Complexes; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D017382:Reactive Oxygen Species; C516138:dorsomorphin; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases