Compound C inhibits hypoxic activation of HIF‐1 independent of AMPK

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.