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

Autor(es)

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]

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] Univ Sao Paulo, Fac Med Sci, Gastroenterol Lab LIM 7, BR-01246000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: DIABETES-METABOLISM RESEARCH AND REVIEWS; v. 29, n. 1, p. 66-76, JAN 2013.
• Citações Web of Science: 19

Resumo

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)

• Processo FAPESP: 09/53192-9 - Influencia da modificacao in vivo da albumina no diabete melito sobre o estresse oxidativo e o estresse do reticulo endoplasmatico em macrofagos - impacto sobre a remocao de colesterol celular
• Beneficiário: Camila Holanda Sartori
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 09/54688-8 - Estresse glicoxidativo e fluxo de lípides em macrófagos: papel dos inibidores de glicação avançada
• Beneficiário: Raphael de Souza Pinto
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• 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
• Modalidade de apoio: 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
• Modalidade de apoio: 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
• Modalidade de apoio: Bolsas no Brasil - Doutorado