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




Advanced Glycation in macrophages induces intracellular accumulation of 7-ketocholesterol and total sterols by decreasing the expression of ABCA-1 and ABCG-1 - Download this document for free, or read online. Document in PDF available to download.

Lipids in Health and Disease

, 10:172

First Online: 29 September 2011Received: 09 September 2011Accepted: 29 September 2011

Abstract

BackgroundAdvanced 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.

MethodsTotal cholesterol and oxysterol subspecies were determined by gas chromatography-mass spectrometry and HDL receptors content by immunoblot.

ResultsIn 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.

ConclusionIn 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.

Keywordsadvanced glycation diabetes mellitus oxysterols 7-ketocholesterol; ABCA-1 ABCG-1 Electronic supplementary materialThe online version of this article doi:10.1186-1476-511X-10-172 contains supplementary material, which is available to authorized users.

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Author: Rodrigo T Iborra - Adriana Machado-Lima - Gabriela Castilho - Valeria S Nunes - Dulcinéia SP Abdalla - Edna R Nakandaka

Source: https://link.springer.com/



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