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http://dx.doi.org/10.5352/JLS.2013.23.5.650

Effects of Lycopene on Endothelial Protein C Receptor Shedding In Vitro and In Vivo  

Yoo, Hayoung (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
Lee, Hyun-Shik (School of Life Sciences, College of Natural Sciences, Kyungpook National University)
Lee, Wonhwa (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
Bae, Jong-Sup (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
Publication Information
Journal of Life Science / v.23, no.5, 2013 , pp. 650-656 More about this Journal
Abstract
Endothelial protein C receptor (EPCR) plays a pivotal role in augmenting Protein C activation through the thrombin-thrombomodulin complex. EPCR activity is markedly changed by ectodomain cleavage and released as the soluble protein (sEPCR). EPCR shedding is mediated by tumor necrosis factor-${\alpha}$ converting enzyme (TACE). Lycopene found in tomatoes and tomato products has anti-oxidant, anti- cancer and anti-inflammatory effects. However, little is known about the effects of lycopene on EPCR shedding. We investigated this issue by monitoring the effects of lycopene on the phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and on the cecal ligation and puncture (CLP)-mediated EPCR shedding. Data showed that lycopene potently inhibited the PMA, TNF-${\alpha}$, IL-$1{\beta}$ and CLP-induced EPCR shedding by suppressing TACE expression. Furthermore, lycopene reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK). Given these results, lycopene should be viewed as a candidate therapeutic agent for the treatment of various severe vascular inflammatory diseases via inhibition of the EPCR shedding.
Keywords
Lycopene; endothelial protein C receptor (EPCR); shedding; phorbol-12-myristate 13-acetate (PMA); cecal ligation and puncture (CLP);
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