Cytoprotection of human endothelial cells from menadione cytotoxicity by caffeic acid phenethyl ester: the role of heme oxygenase-1

Xinyu Wang, Salomon Stavchansky, Baiteng Zhaoa, James A. Bynum, Sean M. Kerwin, Phillip D. Bowman

Research output: Contribution to journalArticlepeer-review

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 languageAmerican English
JournalEuropean journal of pharmacology
Volume591
StatePublished - 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

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