Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
AMP-Activated Protein Kinases
-
Cell Hypoxia
-
Hypoxia-Inducible Factor 1 / antagonists & inhibitors
-
Hypoxia-Inducible Factor 1 / metabolism*
-
Mitochondria / metabolism
-
Multienzyme Complexes / metabolism*
-
Protein Kinase Inhibitors / pharmacology*
-
Protein Serine-Threonine Kinases / metabolism*
-
Pyrazoles / pharmacology*
-
Pyrimidines / pharmacology*
-
Reactive Oxygen Species / metabolism
Substances
-
Hypoxia-Inducible Factor 1
-
Multienzyme Complexes
-
Protein Kinase Inhibitors
-
Pyrazoles
-
Pyrimidines
-
Reactive Oxygen Species
-
dorsomorphin
-
Protein Serine-Threonine Kinases
-
AMP-Activated Protein Kinases