Abstract
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.
Original language | American English |
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Journal | European journal of pharmacology |
Volume | 591 |
State | Published - Jan 1 2008 |
Keywords
- Antioxidants/administration & dosage/pharmacology
- Blotting
- Caffeic Acids/administration & dosage/pharmacology
- Carbon Monoxide/metabolism
- Cells
- Cultured
- Dose-Response Relationship
- Drug
- Endothelial Cells/drug effects/metabolism
- Heme Oxygenase-1/drug effects/metabolism
- Humans
- Oxidative Stress/drug effects
- Phenylethyl Alcohol/administration & dosage/analogs & derivatives/pharmacology
- Reverse Transcriptase Polymerase Chain Reaction
- Umbilical Veins/cytology
- Up-Regulation/drug effects
- Vitamin K 3/toxicity
- Western
Disciplines
- Pharmacy and Pharmaceutical Sciences