[HTML][HTML] A non-hypoxic, ROS-sensitive pathway mediates TNF-α-dependent regulation of HIF-1α

JJ Haddad, SC Land - FEBS letters, 2001 - Elsevier
JJ Haddad, SC Land
FEBS letters, 2001Elsevier
A non-hypoxic, reactive oxygen species (ROS)-sensitive pathway mediating tumor necrosis
factor-α (TNF-α)-dependent regulation of hypoxia-inducible factor-1α (HIF-α) was
investigated in vitro. TNF-α mediated the translocation of HIF-1α, associated with up-
regulating its activity under normoxia. Analysis of the mode of action of TNF-α revealed the
accumulation of hydrogen peroxide (H2O2), superoxide anion (O2−) and hydroxyl radical
(OH). Antioxidants purported as prototypical scavengers of H2O2 and OH, attenuated TNF-α …
A non-hypoxic, reactive oxygen species (ROS)-sensitive pathway mediating tumor necrosis factor-α (TNF-α)-dependent regulation of hypoxia-inducible factor-1α (HIF-α) was investigated in vitro. TNF-α mediated the translocation of HIF-1α, associated with up-regulating its activity under normoxia. Analysis of the mode of action of TNF-α revealed the accumulation of hydrogen peroxide (H2O2), superoxide anion (O2) and hydroxyl radical (OH). Antioxidants purported as prototypical scavengers of H2O2 and OH, attenuated TNF-α-induced HIF-1α activation, and blockading NADPH-oxidase by scavenging O2 reduced the activity of HIF-1α. Inhibition of the mitochondrion complex I abrogated TNF-α-dependent activation of HIF-1α. Interrupting the respiratory chain reversed the excitatory effect of TNF-α on HIF-1α. These results indicate a non-hypoxic pathway mediating cytokine-dependent regulation of HIF-1α in a ROS-sensitive mechanism.
Elsevier