Caffeic acid phenethyl ester is a potent inhibitor of HIF prolyl hydroxylase: structural analysis and pharmacological implication. Export

@article{citeulike:5765767, abstract = {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 (-CC-) 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.}, author = {Choi, Daekyu and Han, Jeongoh and Lee, Youna and Choi, Jungyun and Han, Songyi and Hong, Sungchae and Jeon, Hyunchu and Kim, Young Mi M. and Jung, Yunjin}, citeulike-article-id = {5765767}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jnutbio.2009.06.002}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0955286309001211}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19740641}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19740641}, day = {7}, doi = {10.1016/j.jnutbio.2009.06.002}, issn = {1873-4847}, journal = {The Journal of nutritional biochemistry}, keywords = {cape, herb, hif1, propolis}, month = {September}, posted-at = {2009-09-24 06:11:30}, priority = {2}, title = {Caffeic acid phenethyl ester is a potent inhibitor of HIF prolyl hydroxylase: structural analysis and pharmacological implication.}, url = {http://dx.doi.org/10.1016/j.jnutbio.2009.06.002}, year = {2009} }

TY - JOUR ID - citeulike:5765767 L3 - citeulike-article-id:5765767 N2 - 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 (-CC-) 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. JF - The Journal of nutritional biochemistry SN - 1873-4847 TI - Caffeic acid phenethyl ester is a potent inhibitor of HIF prolyl hydroxylase: structural analysis and pharmacological implication. KW - cape KW - herb KW - hif1 KW - propolis AU - Choi, Daekyu AU - Han, Jeongoh AU - Lee, Youna AU - Choi, Jungyun AU - Han, Songyi AU - Hong, Sungchae AU - Jeon, Hyunchu AU - Kim, Young Mi AU - Jung, Yunjin PY - 2009/09/07/ UR - http://dx.doi.org/10.1016/j.jnutbio.2009.06.002 ER -