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Author Panicker, Sumith R. ♦ Sreenivas, Prethish ♦ Babu, Mani Sankar ♦ Karunagaran, Devarajan ♦ Kartha, C. C.
Source Sree Chitra Tirunal Institute for Medical Sciences & Technology
Content type Text
Publisher Pharmacological Research
File Format PDF
Language English
Subject Domain (in DDC) Natural sciences & mathematics ♦ Life sciences; biology ♦ Physiology & related subjects ♦ Biochemistry ♦ Technology ♦ Medicine & health
Subject Domain (in MeSH) Cells ♦ Anatomy ♦ Heterocyclic Compounds ♦ Carbohydrates ♦ Amino Acids, Peptides, and Proteins ♦ Chemicals and Drugs ♦ Chemical Phenomena ♦ Genetic Phenomena ♦ Biological Sciences
Subject Keyword Biochemistry
Abstract Monocyte Chemoattractant Protein-1 (MCP-1) is involved in the diapedesis of blood monocytes into the arterial intima, an early critical event in atherogenesis. Modulating MCP-1 expression can be a key strategy to decrease the risk for atherosclerosis in diabetes. We hypothesized that quercetin, an anti-inflammatory molecule could modulate high glucose concentration (HG) induced MCP-1 expression in aortic endothelial cells in vitro because of its regulatory effects on Activator Protein-1 (AP-1) and Nuclear Factor-kappa B (NF-kappa B). Rat aortic endothelial cells (RAECs) were exposed to HG in the presence or absence of quercetin. Quercetin attenuated HG induced MCP-1 mRNA (42%) and protein synthesis (45%) when estimated using real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Western blot analysis found quercetin to maintain cytosolic p65 protein levels to that seen in control. Quercetin was found to attenuate HG induced increased NF-kappa B and AP-1 DNA binding activity in electrophoretic mobility shift assay. Immunofluorescence studies revealed quercetin to prevent HG induced nuclear localization of p65 and c-jun. Quercetin was also found to decrease HG induced activation of NF-kappa B (71% +/- 14%), AP-1 (69% +/- 24%) and MCP-1 promoter (79% +/- 25%) in EA.hy926 cells when analyzed using luciferase reporter assay.We conclude that quercetin attenuates MCP-1 expression in HG treated RAECs, probably by regulating both NF-kappa B and AP-1 pathways. The findings provide new insights into HG induced MCP-1 gene regulation in aortic endothelial cells and the potential of quercetin in abating the risk for atherosclerosis in diabetes. (C) 2010 Elsevier Ltd. All rights reserved.
Education Level UG and PG
Learning Resource Type Article
Educational Framework Medical Council of India (MCI)
Journal PHARMACOLOGICAL RESEARCH
Volume Number 62
Issue Number 4
Page Count 9
Starting Page 328
Ending Page 336