Advanced Glycation in macrophages induces intracellular accumulation of 7-ketocholesterol and total sterols by decreasing the expression of ABCA-1 and ABCG-1

Autor(es)

Iborra, Rodrigo T. ^[1] ; Machado-Lima, Adriana ^[1] ; Castilho, Gabriela ^[1] ; Nunes, Valeria S. ^[1] ; Abdalla, Dulcineia S. P. ^[2] ; Nakandakare, Edna R. ^[1] ; Passarelli, Marisa ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Sci, Lipids Lab LIM 10, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: LIPIDS IN HEALTH AND DISEASE; v. 10, SEP 29 2011.
• Citações Web of Science: 15

Resumo

Background: Advanced glycation end products (AGE) alter lipid metabolism and reduce the macrophage expression of ABCA-1 and ABCG-1 which impairs the reverse cholesterol transport, a system that drives cholesterol from arterial wall macrophages to the liver, allowing its excretion into the bile and feces. Oxysterols favors lipid homeostasis in macrophages and drive the reverse cholesterol transport, although the accumulation of 7-ketocholesterol, 7alpha-hydroxycholesterol and 7beta-hydroxycholesterol is related to atherogenesis and cell death. We evaluated the effect of glycolaldehyde treatment (GAD; oxoaldehyde that induces a fast formation of intracellular AGE) in macrophages overloaded with oxidized LDL and incubated with HDL alone or HDL plus LXR agonist (T0901317) in: 1) the intracellular content of oxysterols and total sterols and 2) the contents of ABCA-1 and ABCG-1. Methods: Total cholesterol and oxysterol subspecies were determined by gas chromatography/mass spectrometry and HDL receptors content by immunoblot. Results: In control macrophages (C), incubation with HDL or HDL + T0901317 reduced the intracellular content of total sterols (total cholesterol + oxysterols), cholesterol and 7-ketocholesterol, which was not observed in GAD macrophages. In all experimental conditions no changes were found in the intracellular content of other oxysterol subspecies comparing C and GAD macrophages. GAD macrophages presented a 45% reduction in ABCA-1 protein level as compared to C cells, even after the addition of HDL or HDL + T0901317. The content of ABCG-1 was 36.6% reduced in GAD macrophages in the presence of HDL as compared to C macrophages. Conclusion: In macrophages overloaded with oxidized LDL, glycolaldehyde treatment reduces the HDL-mediated cholesterol and 7-ketocholesterol efflux which is ascribed to the reduction in ABCA-1 and ABCG-1 protein level. This may contribute to atherosclerosis in diabetes mellitus. (AU)

• Processo FAPESP: 10/50108-4 - Glicoxidação intracelular e estresse do retículo endoplasmático: efeito potenciais sobre os transportadores ABCA-1 e sobre o fluxo de lípides em macrófagos
• Beneficiário: Gabriela Castilho
• 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
• 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: 09/53869-9 - 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