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KMID : 0613820130230050650
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Journal of Life Science
2013 Volume.23 No. 5 p.650 ~ p.656
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Effects of Lycopene on Endothelial Protein C Receptor Shedding In Vitro and In Vivo
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Yoo Ha-Young
Lee Hyun-Shik
Lee Won-Hwa
Bae Jong-Sup
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Abstract
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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-α 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)-α, interleukin (IL)-1β and on the cecal ligation and puncture (CLP)-mediated EPCR shedding. Data showed that lycopene potently inhibited the PMA, TNF-α, IL-1β 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.
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KEYWORD
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Lycopene, endothelial protein C receptor (EPCR), shedding, phorbol-12-myristate 13-acetate (PMA), cecal ligation and puncture (CLP)
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