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

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Autor(es):
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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]
Número total de Autores: 16
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: Journal of Cellular Physiology; v. 230, n. 6, p. 1250-1257, JUN 2015.
Citações Web of Science: 10
Resumo

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)

Processo FAPESP: 09/53192-9 - Influência da modificação in vivo da albumina no diabete melito sobre o estresse oxidativo e o estresse do reticulo endoplasmático em macrófagos - impacto sobre a remoção de colesterol celular
Beneficiário:Camila Holanda Sartori
Linha de fomento: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 09/53869-9 - Influência da modificação da albumina no diabete melito sobre a expressão diferencial de genes e o fluxo de lípides em macrófagos
Beneficiário:Marisa Passarelli
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 06/55496-7 - Influência da glicoxidação sobre a expressão diferencial de genes macrófagos e sobre o fluxo de lípides, mediado por HDL
Beneficiário:Adriana Machado Saldiba de Lima
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 09/54688-8 - Estresse glicoxidativo e fluxo de lípides em macrófagos: papel dos inibidores de glicação avançada
Beneficiário:Raphael de Souza Pinto
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 07/59710-6 - Glicação avançada em macrófagos diminui o conteúdo dos receptores de HDL - ABCA-1 e ABCG-1- e induz acúmulo intracelular de 7 -cetocolesterol
Beneficiário:Rodrigo Tallada Iborra
Linha de fomento: Bolsas no Brasil - Doutorado