TABLE 1

Environmental regulator of HIF-1


Regulator

Function/Pathway Involved

Consequence

Reference
Nickel (Ni2+) Decreases cellular Fe level Increased HIF-1α Davidson et al., 2005
Inhibits PHDs
Down-regulates the expression of FIH-1 and ARD1 Ke et al., 2005
Depletes intracellular ascorbate Salnikow et al., 2004
PI3K/Akt Li et al., 2004
Cobalt (Co2+) Replaces Fe Increased HIF-1α Yuan et al., 2003
Down-regulates the expression of FIH-1 and ARD1 Ke et al., 2005
Depletes intracellular ascorbate Salnikow et al., 2004
PI3K Increased HIF-1α Gao et al., 2004
Arsenite ROS Duyndam et al., 2001
p38 MAPK Duyndam et al., 2003
Chromium p38 MAPK, ROS Increased HIF-1α Gao et al., 2004
PI3K/Akt, ROS Increased HIF-1α Gao et al., 2002
Vanadate AMP-activated protein kinase (AMPK) Hwang et al., 2004
Desferrioxamine (DFO) Fe chelator Increased HIF-1α Wang and Semenza, 1993
Insulin Interleukin-1 (IL-1) PI3K Increased HIF-1α Stiehl et al., 2002
Insulin-like growth factor (IGF)-1, IGF-2 ROS Increased HIF-1α Feldser et al., 1999
Fetal calf serum ROS Increased HIF-1α Richard et al., 2000
Angiotensin II (Ang II) ROS Increased HIF-1α Gorlach et al., 2001
Thrombin, Platelet-derived growth factor (PDGF)
Nitric oxide (NO) MAPK, PI3K Increased HIF-1α Kasuno et al., 2004
Inhibits PHDs Metzen et al., 2003b
Nitric oxide (NO) under hypoxia Inhibits mitochondrial O2 consumption Decreased HIF-1α Hagen et al., 2003
Increases intracellular Fe and PHDs activity Callapina et al., 2005
TGF-α ROS Increased HIF-1α translocation and activity Haddad and Land, 2001


Increased DNA binding
Hellwig-Burgel et al., 1999