Cytoprotection of human endothelial cells from menadione cytotoxicity by caffeic acid phenethyl ester: the role of heme oxygenase-1.
Caffeic acid phenethyl ester (CAPE), derived from various plant sources, has been shown to ameliorate ischemia/reperfusion injury in vivo, and this has been attributed to its ability to reduce oxidative stress. Here we investigated the cytoprotection of CAPE against menadione-induced oxidative stress in human umbilical vein endothelial cells (HUVEC) to evaluate potential gene expression involvement. CAPE exhibited dose-dependent cytoprotection of HUVEC. A gene screen with microarrays was performed to identify the potential cytoprotective gene(s) induced by CAPE. Heme oxygenase-1 (HO-1) was highly upregulated by CAPE and this was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting. Inhibition of HO-1 activity using the HO-1 inhibitor tin protoporphyrin IX (SnPPIX), resulted in loss of cytoprotection. Carbon monoxide, one of HO-1 catabolic products appeared to play a small role in CAPE protection. Caffeic acid, a potential metabolite of CAPE with similar free radical scavenging ability, however, didn't show any cytoprotective effect nor induce HO-1. These findings suggest an important role of HO-1 induction in CAPE cytoprotection against oxidant stress, which may not relate to CAPE structural antioxidant activity nor to its traditional enzymatic activity in decomposing heme but to a yet to be determined activity.
College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, USA.
Xinyu
X
Wang
Salomon
S
Stavchansky
Baiteng
B
Zhao
James A
JA
Bynum
Sean M
SM
Kerwin
Phillip D
PD
Bowman
D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D015153:Blotting, Western; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects; D024483:Vitamin K 3 / Q000633:toxicity
D000975:Antioxidants; D002109:Caffeic Acids; D024483:Vitamin K 3; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; C040048:caffeic acid