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Table 1 Modes of HIF signal enhancement

From: Hypoxia-inducible factors and the prevention of acute organ injury

Stimulus/Agent

Remarks

Potential Clinical Applications

Inhibition of PHDs by the induction of cellular physiologic hypoxia

  

   Hypoxic chamber (e.g., 8% O2 in ambient air)

depressed systemic PO2

 

   Carbon monoxide admixture to ambient air

functional anemia normal systemic PO2

✓

   Anemia

 

normal systemic PO2

   Arterial clamping

 

normal systemic PO2

Chemical inhibition of PHDs by hypoxia-mimetics

  

   CoCl2 (interferes with Fe2+)

non-specific

 

   Mimosine (2-oxoglutarate analogue)

non-specific

 

   Other patented PHD inhibitors

specific

✓

Molecular biology techniques

  

   Von-Hippel-Lindau knockout

non-specific

 

   PHD siRNA transfection

PHD-specific

 

   Constitutively active HIF-α transgenes

organ-specific

✓

  1. PHD: prolyl hydroxylase domain enzyme