PMID- 17655880 OWN - NLM STAT- MEDLINE DCOM- 20071003 LR - 20131121 IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 81 IP - 7 DP - 2007 Jul 26 TI - D-Psicose inhibits the expression of MCP-1 induced by high-glucose stimulation in HUVECs. PG - 592-9 AB - 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. FAU - Murao, Koji AU - Murao K AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan. mkoji@kms.ac.jp FAU - Yu, Xiao AU - Yu X FAU - Cao, Wen M AU - Cao WM FAU - Imachi, Hitomi AU - Imachi H FAU - Chen, Ke AU - Chen K FAU - Muraoka, Tomie AU - Muraoka T FAU - Kitanaka, Noriko AU - Kitanaka N FAU - Li, Junhun AU - Li J FAU - Ahmed, Rania A M AU - Ahmed RA FAU - Matsumoto, Kensuke AU - Matsumoto K FAU - Nishiuchi, Takamasa AU - Nishiuchi T FAU - Tokuda, Masaaki AU - Tokuda M FAU - Ishida, Toshihiko AU - Ishida T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070703 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Chemokine CCL2) RN - 0 (RNA, Messenger) RN - 23140-52-5 (psicose) RN - 30237-26-4 (Fructose) RN - EC 1.13.12.- (Luciferases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Cells, Cultured MH - Chemokine CCL2/*antagonists & inhibitors/biosynthesis/genetics MH - Endothelial Cells/*drug effects MH - Enzyme-Linked Immunosorbent Assay MH - Fructose/*pharmacology MH - Gene Expression Regulation/drug effects MH - Genes, Reporter/genetics MH - Glucose/*pharmacology MH - Humans MH - Immunohistochemistry MH - Luciferases/biosynthesis/genetics MH - Phosphorylation MH - Plasmids/genetics MH - RNA, Messenger/biosynthesis/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction/drug effects MH - Stimulation, Chemical MH - p38 Mitogen-Activated Protein Kinases/metabolism EDAT- 2007/07/28 09:00 MHDA- 2007/10/04 09:00 CRDT- 2007/07/28 09:00 PHST- 2007/02/13 00:00 [received] PHST- 2007/06/06 00:00 [revised] PHST- 2007/06/24 00:00 [accepted] PHST- 2007/07/28 09:00 [pubmed] PHST- 2007/10/04 09:00 [medline] PHST- 2007/07/28 09:00 [entrez] AID - S0024-3205(07)00483-3 [pii] AID - 10.1016/j.lfs.2007.06.019 [doi] PST - ppublish SO - Life Sci. 2007 Jul 26;81(7):592-9. doi: 10.1016/j.lfs.2007.06.019. Epub 2007 Jul 3.