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

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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]
Total Authors: 7
[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
Total Affiliations: 2
Document type: Journal article
Source: LIPIDS IN HEALTH AND DISEASE; v. 10, SEP 29 2011.
Web of Science Citations: 15

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)

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