title: D-Psicose inhibits the expression of MCP-1 induced by high-glucose stimulation in HUVECs.
abstract: Monocyte chemoattractant protein-1 (MCP-1) is a 76-amino-acid chemokine thought to be the major chemotactic factor for monocytes. MCP-1 is found in macrophage-rich areas of atherosclerotic lesions. Recent report indicates that MCP-1 is induced by glucose-stimulation, raising the important link between diabetes mellitus and atherosclerosis. One of the rare sugars, d-psicose (d-ribo-2-hexulose) is present in small quantities in commercial carbohydrate complexes, however the physiological functions of d-psicose have not been evaluated. In this study, we examined the effects of d-psicose on MCP-1 expression in human umbilical vein endothelial cells (HUVECs). Results showed that MCP-1 mRNA and protein were stimulated following exposure to 22.4 mM glucose. Transcriptional activity of MCP-1 promoter paralleled endogenous expression of the gene and this activity was dependent on the dose of d-glucose. d-Psicose inhibited these effects. Next we used inhibitors of selected signal transduction pathways to show that high-glucose (HG) stimulated MCP-1 promoter activity was sensitive to p38-Mitogen-Activated Protein Kinase (p38-MAPK) pathway inhibitor. As expected, a dominant-negative p38-MAPK abolished the stimulatory effect of HG on the promoter activity. To incubate the cells with HG and d-psicose reduced the activation of p38-MAPK. Together, these results indicate that the d-psicose suppression of HG induced MCP-1 expression is mediated in part by inhibition of the p38-MAPK pathway and raise the possibility that d-psicose may be of therapeutic value in the treatment of diseases such as atherosclerosis.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan. mkoji@kms.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Murao
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.forename: Wen M
authors.initials: WM
authors.lastname: Cao
authors.forename: Hitomi
authors.initials: H
authors.lastname: Imachi
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Tomie
authors.initials: T
authors.lastname: Muraoka
authors.forename: Noriko
authors.initials: N
authors.lastname: Kitanaka
authors.forename: Junhun
authors.initials: J
authors.lastname: Li
authors.forename: Rania A M
authors.initials: RA
authors.lastname: Ahmed
authors.forename: Kensuke
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Takamasa
authors.initials: T
authors.lastname: Nishiuchi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tokuda
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ishida
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005632:Fructose / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D012333:RNA, Messenger; C003243:psicose; D005632:Fructose; D008156:Luciferases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose