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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Advanced glycated albumin isolated from poorly controlled type 1 diabetes mellitus patients alters macrophage gene expression impairing ABCA-1-mediated reverse cholesterol transport

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Machado-Lima, Adriana [1] ; Iborra, Rodrigo T. [1] ; Pinto, Raphael S. [1] ; Sartori, Camila H. [1] ; Oliveira, Erika R. [2] ; Nakandakare, Edna R. [1] ; Stefano, Jose T. [3] ; Giannella-Neto, Daniel [3] ; Correa-Giannella, Maria Lucia C. [2] ; Passarelli, Marisa [1]
Total Authors: 10
[1] Univ Sao Paulo, Fac Med Sci, Lipids Lab LIM 10, BR-01246000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med Sci, Cellular & Mol Endocrinol Lab LIM 25, BR-01246000 Sao Paulo - Brazil
[3] Univ Sao Paulo, Fac Med Sci, Gastroenterol Lab LIM 7, BR-01246000 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: DIABETES-METABOLISM RESEARCH AND REVIEWS; v. 29, n. 1, p. 66-76, JAN 2013.
Web of Science Citations: 19

Background We evaluated the effects of albumin isolated from control individuals and from patients with poorly controlled type 1 diabetes mellitus on macrophage gene expression and on reverse cholesterol transport. Methods Serum albumin was purified from control subjects (n = 12) and from patients with poorly controlled type 1 diabetes mellitus (n = 13). 14C-cholesterol-labelled J774 macrophages treated with albumin were employed to measure cholesterol efflux mediated by apo A-I, HDL3 or HDL2, the intracellular lipid accumulation and the cellular ABCA-1 protein content. Agilent arrays (44000 probes) were used to analyse gene expression. Several differentially expressed genes were validated by real-time reverse transcription-PCR using TaqMan Two Step RT-PCR. Results Levels of glycation-modified and (carboxymethyl)lysine-modified albumin were higher in diabetic patients than in control subjects. Apo A-I-mediated and HDL2-mediated cellular cholesterol efflux were impaired in macrophages treated with albumin from diabetic patients in comparison with control albumin-treated cells, which was attributed to the reduction in ABCA-1 protein content. Even in the presence of cholesterol acceptors, a higher level of intracellular lipid was observed in macrophages exposed to albumin from diabetic individuals in comparison with the control. The reduction in ABCA-1 content was associated with enhanced expression of stearoyl CoA desaturase 1 and decreased expression of janus kinase 2, which were induced by albumin from patients with type 1 diabetes mellitus. Conclusions (Carboxymethyl)lysine-modified albumin isolated from poorly controlled type 1 diabetic patients impairs ABCA-1-mediated reverse cholesterol transport and elicits intracellular lipid accumulation, possibly contributing to atherosclerosis. Copyright (C) 2012 John Wiley \& Sons, Ltd. (AU)

FAPESP's process: 09/53869-9 - Influence of modified albumin from Diabetes mellitus in the differential expression of genes and lipid flux in macrophages: the role of reactive oxygen species, inflammatory markers and endoplasmic reticulum stress
Grantee:Marisa Passarelli
Support Opportunities: Regular Research Grants
FAPESP's process: 07/59710-6 - Advanced glycation in macrophages decreases the content of the HDL - ABCA-1 and ABCG-1 - receptors and induces intracellular 7-ketocholesterol accumulation
Grantee:Rodrigo Tallada Iborra
Support Opportunities: Scholarships in Brazil - Doctorate