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Involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin

Grant number: 13/06800-9
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): June 01, 2013
Effective date (End): August 31, 2013
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Marisa Passarelli
Grantee:Adriana Machado Saldiba de Lima
Supervisor: Ann Marie Schmidt
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: NYU Langone Medical Center, United States  
Associated to the scholarship:12/19112-0 - Involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin - contribution of glycemic control in diabetes mellitus., BP.PD

Abstract

Advanced glycation end products (AGE) are elevated in diabetes mellitus (DM) and predict the development of atherosclerosis independently of other risk factors. AGE induce the generation of oxygen reactive species (ROS) and inflammatory markers related to long term complications of DM. We recently demonstrated that advanced glycated albumin (AGE albumin) - isolated from poorly controlled DM patients - reduces the expression of the HDL receptor, ABCA-1, leading to cholesterol accumulation in macrophages. Our hypothesis is that the effects of AGE albumin in cholesterol accumulation in macrophages can be mediated by the interaction between the receptor for AGE (RAGE). Then, we intend to investigate the effect of RAGE in ROS generation, NF-kB expression, ABCA-1 expression and cholesterol efflux mediated by apo A-1, HDL2 and HDL3 in macrophages treated with control (C) albumin, glycated (AGE) albumin (produced in vitro by incubation with glycolaldehydo) and albumin isolated from poorly glycemic control DM subjects (HbA1c > 8%). For this, RAGE null cells or macrophages treated with soluble RAGE will be treated with C albumin, AGE albumin or albumin isolated from poorly controlled DM subjects in order to investigate: ROS generation and ABCA-1 protein content by flow cytometry, NF-kB activity by Immunocytochemistry and cholesterol efflux by labeled cells with 14C-cholesterol. Findings will help to elucidate the participation of the AGE/RAGE axis in cellular lipid flux in DM that can contribute to therapeutic interventions. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MACHADO-LIMA, ADRIANA; LOPEZ-DIEZ, RAQUEL; IBORRA, RODRIGO TALLADA; PINTO, RAPHAEL DE SOUZA; DAFFU, GURDIP; SHEN, XIAOPING; NAKANDAKARE, EDNA REGINA; MACHADO, UBIRATAN FABRES; CORREA-GIANNELLA, MARIA LUCIA CARDILLO; SCHMIDT, ANN MARIE; et al. RAGE Mediates Cholesterol Efflux Impairment in Macrophages Caused by Human Advanced Glycated Albumin. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 19, . (12/19112-0, 15/21072-5, 13/06800-9, 18/00172-0, 13/26256-1, 12/12088-7, 14/05951-6, 16/15603-0)

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