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

In Type 2 Diabetes Mellitus Glycated Albumin Alters Macrophage Gene Expression Impairing ABCA1-Mediated Cholesterol Efflux

Full text
Author(s):
Show less -
Machado-Lima, Adriana [1] ; Iborra, Rodrigo T. [1] ; Pinto, Raphael S. [1] ; Castilho, Gabriela [1] ; Sartori, Camila H. [1] ; Oliveira, Erika R. [2] ; Okuda, Ligia S. [1] ; Nakandakare, Edna R. [1] ; Giannella-Neto, Daniel [3] ; Machado, Ubiratan F. [4] ; Correa-Giannella, Maria Lucia C. [2] ; Traldi, Pietro [5] ; Porcu, Simona [6] ; Roverso, Marco [6] ; Lapolla, Annunziata [6] ; Passarelli, Marisa [1]
Total Authors: 16
Affiliation:
[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] Uninove, Sao Paulo - Brazil
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-01246000 Sao Paulo - Brazil
[5] ISTM CNR, Padua - Italy
[6] Univ Padua, Dept Med, Padua - Italy
Total Affiliations: 6
Document type: Journal article
Source: Journal of Cellular Physiology; v. 230, n. 6, p. 1250-1257, JUN 2015.
Web of Science Citations: 10
Abstract

Advanced glycation end products (AGE) are elevated in diabetes mellitus (DM) and predict the development of atherosclerosis. AGE-albumin induces oxidative stress, which is linked to a reduction in ABCA-1 and cholesterol efflux. We characterized the glycation level of human serum albumin (HSA) isolated from poorly controlled DM2 (n=11) patients compared with that of control (C, n=12) individuals and determined the mechanism by which DM2-HSA can interfere in macrophage lipid accumulation. The HSA glycation level was analyzed by MALDI/MS. Macrophages were treated for 18h with C- or DM2-HSA to measure the C-14-cholesterol efflux, the intracellular lipid accumulation and the cellular ABCA-1 protein content. Agilent arrays (44000 probes) were used to analyze gene expression, and the differentially expressed genes were validated by real-time RT-PCR. An increased mean mass was observed in DM2-HSA compared with C-HSA, reflecting the condensation of at least 5 units of glucose. The cholesterol efflux mediated by apo AI, HDL3, and HDL2 was impaired in DM2-HSA-treated cells, which was related to greater intracellular lipid accumulation. DM2-HSA decreased Abcg1 mRNA expression by 26%. Abca1 mRNA was unchanged, although the final ABCA-1 protein content decreased. Compared with C-HAS-treated cells, NADPH oxidase 4 mRNA expression increased in cells after DM2-HSA treatment. Stearoyl-Coenzyme A desaturase 1, janus kinase 2, and low density lipoprotein receptor mRNAs were reduced by DM2-HSA. The level of glycation that occurs in vivo in DM2-HSA-treated cells selectively alters macrophage gene expression, impairing cholesterol efflux and eliciting intracellular lipid accumulation, which contribute to atherogenesis, in individuals with DM2. J. Cell. Physiol. XXXX: XX-XX, 2015. (c) 2015 Wiley Periodicals, Inc. J. Cell. Physiol. 230: 1250-1257, 2015. (c) 2014 Wiley Periodicals, Inc., A Wiley Company (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