Receptor of Advanced Glycation End Products (RAGE) Positively Regulates CD36 Expression and Reactive Oxygen Species Production in Human Monocytes in Diabetes

Introduction: Advanced glycation end products (AGEs) engagement of a monocyte surface receptor (RAGE) induces atherosclerosis. AGEs also act as CD36 ligands. We studied reactive oxygen species (ROS) and CD36 expression after siRNA inhibition of RAGE expression in human monocytes. Methods: We isolated monocytes from: a) 10 type 2 diabetics, and b) 5 age- and sex-matched healthy individuals. CD36 expression and ROS production were evaluated before and after RAGE knockdown. Results: After incubation of monocytes with AGE + bovine serum albumin (BSA), CD36 expression and intracellular ROS increased significantly in all groups. In RAGE-knockdown monocytes, AGE-induced CD36 expression and ROS generation were also significantly inhibited. Conclusions: Blocking RAGE expression using siRNA in human monocytes led to a significant inhibition of CD36 expression and ROS production, suggesting a positive interaction between RAGE, CD36 expression and ROS generation in monocytes.

[1]  D. Mikhailidis,et al.  Evaluation of the effect of oxidative stress and vitamin E supplementation on renal function in rats with streptozotocin-induced Type 1 diabetes. , 2009, Journal of diabetes and its complications.

[2]  M. Grillo,et al.  Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases , 2008, Amino Acids.

[3]  Su-Yen Goh,et al.  The role of advanced glycation end products in progression and complications of diabetes , 2008 .

[4]  R. Ramasamy,et al.  Mechanisms of Disease: advanced glycation end-products and their receptor in inflammation and diabetes complications , 2008, Nature Clinical Practice Endocrinology &Metabolism.

[5]  H. Ruohola-Baker,et al.  Small RNAs: Keeping Stem Cells in Line , 2008, Cell.

[6]  K. Moore,et al.  Macrophage-derived foam cells in atherosclerosis: lessons from murine models and implications for therapy. , 2007, Current drug targets.

[7]  Juliette Martin,et al.  CD36 and macrophages in atherosclerosis. , 2007, Cardiovascular research.

[8]  G. Freund,et al.  Phagocytosis of Cholesteryl Ester Is Amplified in Diabetic Mouse Macrophages and Is Largely Mediated by CD36 and SR-A , 2007, PloS one.

[9]  K. Griendling,et al.  Nox1-based NADPH oxidase-derived superoxide is required for VSMC activation by advanced glycation end-products. , 2007, Free radical biology & medicine.

[10]  Zhenqi Shi,et al.  Development and validation of vectors containing multiple siRNA expression cassettes for maximizing the efficiency of gene silencing , 2006, BMC biotechnology.

[11]  G. Yen,et al.  Effects of flavonoids on the expression of the pro-inflammatory response in human monocytes induced by ligation of the receptor for AGEs. , 2006, Molecular nutrition & food research.

[12]  S. Vannucci,et al.  Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. , 2005, Glycobiology.

[13]  T. Imaizumi,et al.  Diabetic vascular complications: pathophysiology, biochemical basis and potential therapeutic strategy. , 2005, Current pharmaceutical design.

[14]  H. Vlassara Advanced Glycation in Health and Disease: Role of the Modern Environment , 2005, Annals of the New York Academy of Sciences.

[15]  B. Premack,et al.  Method for large scale isolation, culture and cryopreservation of human monocytes suitable for chemotaxis, cellular adhesion assays, macrophage and dendritic cell differentiation. , 2004, Journal of immunological methods.

[16]  S. Horiuchi,et al.  Scavenger receptors for oxidized and glycated proteins , 2003, Amino Acids.

[17]  P. Sharp,et al.  Serum levels of low molecular weight advanced glycation end products in diabetic subjects , 2003, Diabetic medicine : a journal of the British Diabetic Association.

[18]  Tingjun Hou,et al.  ADME evaluation in drug discovery , 2002, Journal of molecular modeling.

[19]  T. Kislinger,et al.  RAGE Blockade Stabilizes Established Atherosclerosis in Diabetic Apolipoprotein E–Null Mice , 2002, Circulation.

[20]  M. Peppa,et al.  Oxidative Stress-Inducing Carbonyl Compounds From Common Foods: Novel Mediators of Cellular Dysfunction , 2002, Molecular medicine.

[21]  M. Crow,et al.  Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-kappaB transcriptional activation and cytokine secretion. , 2001, Diabetes.

[22]  Hiroyuki Arai,et al.  CD36, a Member of the Class B Scavenger Receptor Family, as a Receptor for Advanced Glycation End Products* , 2001, The Journal of Biological Chemistry.

[23]  N. Taniguchi,et al.  Glycoxidation and lipid peroxidation of low-density lipoprotein can synergistically enhance atherogenesis. , 2001, Cardiovascular research.

[24]  A. Hata,et al.  Advanced glycation end products-induced gene expression of scavenger receptors in cultured human monocyte-derived macrophages. , 2000, Biochemical and biophysical research communications.

[25]  M. Neurath,et al.  RAGE Mediates a Novel Proinflammatory Axis A Central Cell Surface Receptor for S100/Calgranulin Polypeptides , 1999, Cell.

[26]  T. Miyata,et al.  Plasma levels of pentosidine in diabetic patients: an advanced glycation end product. , 1998, Journal of the American Society of Nephrology : JASN.

[27]  V. Monnier,et al.  Pentosidine Formation in Skin Correlates With Severity of Complications in Individuals With Long-Standing IDDM , 1992, Diabetes.

[28]  J. Baynes,et al.  Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. , 1991, The Journal of biological chemistry.

[29]  L. Monnier,et al.  Modulation of CD36 protein expression by AGEs and insulin in aortic VSMCs from diabetic and non-diabetic rats. , 2008, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[30]  R. Silverstein,et al.  CD36: implications in cardiovascular disease. , 2007, The international journal of biochemistry & cell biology.

[31]  T. Imaizumi,et al.  Advanced glycation end products (AGEs) and diabetic vascular complications. , 2005, Current diabetes reviews.

[32]  V. Jakuš,et al.  Advanced glycation end-products and the progress of diabetic vascular complications. , 2004, Physiological research.

[33]  M. Brownlee Insight Review Articles , 2022 .