Hypoxia Induces Expression and Activation of AMPK in Rat Dental Pulp Cells

Abstract

AMP-activated protein kinase (AMPK) is a stress-responsive enzyme involved in cell adaptation to an energy crisis. We hypothesized that hypoxia suppresses oxidative phosphorylation and ATP production, resulting in AMPK activation to protect cells. We investigated the effects of hypoxia on cell proliferation, the expression of AMPK and hypoxia-inducible factor 1α (HIF-1α), the activation of AMPK, and the relationship between AMPK and HIF-1α expression in rat dental pulp RPC-C2A cells. AMPK in the cells was composed of catalytic α1, and regulatory β1 and γ1 subunit isoforms. Cell proliferation was initially suppressed under hypoxia, but it increased thereafter, together with an increase in the expression of AMPK and HIF-1α, and the activation of AMPK. Down-regulation of AMPKα1 by siRNA inhibited cell proliferation under both normoxia and hypoxia, revealing that AMPK induction and activation were required for cell proliferation, although HIF-1α expression under hypoxia was not affected.