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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 Glycated apoA-IV Loses Its Ability to Prevent the LPS-Induced Reduction in Cholesterol Efflux-Related Gene Expression in Macrophages

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Okuda, Ligia Shimabukuro [1] ; Iborra, Rodrigo Tallada [2, 1] ; Ramos, Paula [1] ; Machado, Ubiratan Fabres [3] ; Correa-Giannella, Maria Lucia [4, 5] ; Pickford, Russell [6] ; Woods, Tom [7] ; Brimble, Margaret Anne [7] ; Rye, Kerry-Anne [8] ; Passarelli, Marisa [4, 1]
Total Authors: 10
[1] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Lab Lipides LIM 10, Sao Paulo - Brazil
[2] Univ Sao Judas Tadeu, Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil
[4] Univ Nove de Julho, Programa Posgrad Med, Sao Paulo - Brazil
[5] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Lab Carboidratos & Radioimunoensaio LIM 18, Sao Paulo - Brazil
[6] Univ New South Wales, Bioanalyt Mass Spectrometry Facil, Sydney, NSW - Australia
[7] Univ Auckland, Sch Chem Sci, Auckland - New Zealand
[8] Univ New South Wales, Sch Med Sci, Lipid Res Grp, Sydney, NSW - Australia
Total Affiliations: 8
Document type: Journal article
Source: Mediators of Inflammation; v. 2020, JAN 14 2020.
Web of Science Citations: 0

We addressed how advanced glycation (AGE) affects the ability of apoA-IV to impair inflammation and restore the expression of genes involved in cholesterol efflux in lipopolysaccharide- (LPS-) treated macrophages. Recombinant human apoA-IV was nonenzymatically glycated by incubation with glycolaldehyde (GAD), incubated with cholesterol-loaded bone marrow-derived macrophages (BMDMs), and then stimulated with LPS prior to measurement of proinflammatory cytokines by ELISA. Genes involved in cholesterol efflux were quantified by RT-qPCR, and cholesterol efflux was measured by liquid scintillation counting. Carboxymethyllysine (CML) and pyrraline (PYR) levels, determined by Liquid Chromatography-Mass Spectrometry (LC-MS/MS), were greater in AGE-modified apoA-IV (AGE-apoA-IV) compared to unmodified-apoA-IV. AGE-apoA-IV inhibited expression of interleukin 6 (Il6), TNF-alpha (Tnf), IL-1 beta (Il1b), toll-like receptor 4 (Tlr4), tumor necrosis factor receptor-associated factor 6 (Traf6), Janus kinase 2/signal transducer and activator of transcription 3 (Jak2/Stat3), nuclear factor kappa B (Nfkb), and AGE receptor 1 (Ddost) as well as IL-6 and TNF-alpha secretion. AGE-apoA-IV alone did not change cholesterol efflux or ABCA-1 levels but was unable to restore the LPS-induced reduction in expression of Abca1 and Abcg1. AGE-apoA-IV inhibited inflammation but lost its ability to counteract the LPS-induced changes in expression of genes involved in macrophage cholesterol efflux that may contribute to atherosclerosis. (AU)

FAPESP's process: 13/23392-1 - Anti-inflammatory function of apolipoprotein A-IV in diabetes mellitus and its effects on reverse cholesterol transport from macrophages: influence of modification by advanced glycation
Grantee:Ligia Shimabukuro Okuda
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health
Grantee:Ubiratan Fabres Machado
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/21072-5 - Influency of the glycemic control and nefropathy stage on the reverse cholesterol transport in Diabetes mellitus: role of metabolic memory induced by advanced glycated albumin
Grantee:Marisa Passarelli
Support type: Regular Research Grants
FAPESP's process: 13/02854-7 - Anti-inflammatory role of apolipoprotein A-IV in diabetes mellitus and its impact on macrophage reverse cholesterol transport: influence of advanced glycation
Grantee:Ligia Shimabukuro Okuda
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/26256-1 - Intracellular trafficking of HDL receptor - ABCA-1 - in macrophages treated with advanced glycated albumin: influence of glycemic control in reverse cholesterol transport
Grantee:Rodrigo Tallada Iborra
Support type: Scholarships abroad - Research Internship - Post-doctor