Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.14.11.2 (
prolyl hydroxylase
)
1,814
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Caffeic acid phenethyl ester
(
CAPE
) is an active component of propolis from honeybee. We investigated a potential molecular mechanism underlying a
CAPE
-mediated protective effect against ischemia/reperfusion (I/R) injury and analyzed the structure contributing to the
CAPE
effect.
CAPE
induced hypoxia-inducible factor-1 (HIF-1) alpha protein, concomitantly transactivating the HIF-1 target genes vascular endothelial growth factor and heme oxygenase-1, which play a protective role in I/R injury.
CAPE
delayed the degradation of HIF-1alpha protein in cells, which occurred by inhibition of HIF
prolyl hydroxylase
(HPH), the key enzyme for von Hippel-Lindau-dependent HIF-1alpha degradation.
CAPE
inhibition of HPH and induction of HIF-1alpha protein were neutralized by an elevated dose of iron. The catechol moiety, a chelating group, is essential for HPH inhibition, while hydrogenation of the double bond (-C=C-) in the Michael reaction acceptor markedly reduced potency. Removal of the phenethyl moiety of
CAPE
(substitution with the methyl moiety) severely deteriorated its inhibitory activity for HPH. Our data suggest that a beneficial effect of
CAPE
on I/R injury may be ascribed to the activation of HIF-1 pathway via inhibition of HPH and reveal that the chelating moiety of
CAPE
acted as a pharmacophore while the double bond and phenethyl moiety assisted in inhibiting HPH.
...
PMID:Caffeic acid phenethyl ester is a potent inhibitor of HIF prolyl hydroxylase: structural analysis and pharmacological implication. 1974 Jun 41
