QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lei, Y.-P. Articles by Lii, C.-K. Search for Related Content PubMed PubMed Citation Articles by Lei, Y.-P. Articles by Lii, C.-K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DIALLYL DISULFIDE

---

Biochemical, Molecular, and Genetic Mechanisms

Diallyl Disulfide and Diallyl Trisulfide Suppress Oxidized LDL–Induced Vascular Cell Adhesion Molecule and E-Selectin Expression through Protein Kinase A– and B–Dependent Signaling Pathways^1,2

³ Department of Nutrition, Chung Shan Medical University, Taichung 402, Taiwan; ⁴ Department of Nutrition, China Medical University, Taichung 404, Taiwan; and ⁵ Graduate Institute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan

^* To whom correspondence should be addressed. E-mail: cklii{at}csmu.edu.tw.

Uptake of oxidized LDL (ox-LDL) by vascular endothelial cells is a critical step in the initiation and development of atherosclerosis. Adhesion molecules are upregulated by ox-LDL and numerous inflammatory cytokines and play a pivotal role in atherogenesis. In this study, we examined whether diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), 3 major organosulfur compounds of garlic oil, reduce adhesion molecule expression induced by ox-LDL and, if so, through what mechanism. Human umbilical vein endothelial cells were preincubated with 1 mmol/L DAS, 200 µmol/L DADS, or 100 µmol/L DATS for 16 h and then with 40 mg/L ox-LDL for an additional 24 h. ox-LDL induction of cellular and cell surface expression of E-selectin and vascular cell adhesion molecule (VCAM)-1 was suppressed by garlic allyl sulfides in the order DATS > DADS > DAS. The adhesion of HL-60 cells to endothelial cells was inhibited 27 and 33% and the production of cellular peroxides was inhibited 43 and 50% by DADS and DATS, respectively (P < 0.05). ox-LDL alone dephosphorylated protein kinase B (PKB) and cAMP responsive element binding protein (CREB); such deactivation was reversed by DADS and DATS. Electrophoretic mobility shift assay showed that the activation of CREB binding to DNA was consistent with changes in CREB phosphorylation. The protein kinase A (PKA) inhibitor H89 reversed the suppression of VCAM-1 by DADS and DATS, but the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin had no effect. In contrast, wortmannin abolished DADS- and DATS-induced suppression of ox-LDL–induced E-selectin expression. These results suggest that the suppression of ox-LDL–induced E-selectin and VCAM-1 expression by DADS and DATS and, thus, monocyte adhesion to endothelial cells is likely dependent on the PI3K/PKB or PKA/CREB signaling pathway in an adhesion molecule-specific manner. To our knowledge, this is the first report that garlic modulates ox-LDL–mediated leukocyte adhesion to human endothelial cells through the PKB and PKA pathways.