Sulforaphane inhibits endothelial protein C receptor shedding in vitro and in vivo.

Abstract

Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. Increasing evidence has demonstrated that beyond its role in the activation of protein C, endothelial cell protein C receptor (EPCR) is also involved in vascular inflammation. EPCR activity is markedly changed by ectodomain cleavage and its release as the soluble EPCR. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). However, little is known about the effects of SFN on EPCR shedding. Our results demonstrated that SFN induced potent inhibition of phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-α-, interleukin (IL)-1β, and cecal ligation and puncture (CLP)-induced EPCR shedding. SFN also inhibited the expression and activity of PMA-induced TACE in endothelial cells. In addition, treatment with SFN resulted in reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). These results demonstrate the potential of SFN as an anti-sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding.

• Authors: Sae-Kwang Ku, Min-Su Han, Jong-Sup Bae
• Journal: Vascular pharmacology (Vascul Pharmacol) Vol. 63 Issue 1 Pg. 13-8 (Oct 2014) ISSN: 1879-3649 [Electronic] United States
• PMID: 25016099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Blood Coagulation Factors
• Interleukin-1beta
• Isothiocyanates
• Receptors, Cell Surface
• Sulfoxides
• Tumor Necrosis Factor-alpha
• activated protein C receptor
• ADAM Proteins
• ADAM17 Protein
• ADAM17 protein, human
• Adam17 protein, mouse
• sulforaphane
• Tetradecanoylphorbol Acetate

Topics

• ADAM Proteins (metabolism)
• ADAM17 Protein
• Animals
• Blood Coagulation Factors (metabolism)
• Cecum (injuries)
• Disease Models, Animal
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• In Vitro Techniques
• Interleukin-1beta (metabolism)
• Isothiocyanates (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Receptors, Cell Surface (metabolism)
• Sepsis (drug therapy, physiopathology)
• Sulfoxides
• Tetradecanoylphorbol Acetate (pharmacology)
• Tumor Necrosis Factor-alpha