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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: Mediators of Inflammation; v. 2020, JAN 14 2020.
• Web of Science Citations: 0

Abstract

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