Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?

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RESEARCH PRODUCT

Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?

Guillermo Raúl Schinella Nahuel A. Ramella Nahuel A. Ramella José Luis Ríos M. Alejandra Tricerri M. Alejandra Tricerri Isabel Andújar Silvana Antonia Rosu Silvana Antonia Rosu

subject

0301 basic medicine Lipopolysaccharide MACROPHAGES ACTIVATION Mutant Stimulation Inflammation Oxidative phosphorylation Pathology and Forensic Medicine Ciencias Biológicas 03 medical and health sciences chemistry.chemical_compound INFLAMMATION Physiology (medical)APOLIPOPROTEIN A-I VARIANTS medicine NUCLEAR FACTOR-ΚB chemistry.chemical_classification Reactive oxygen species Amyloidosis NF-κB Bioquímica y Biología Molecular medicine.disease Cell biology 030104 developmental biology chemistry AMYLOIDOSIS lipids (amino acids peptides and proteins)medicine.symptom CIENCIAS NATURALES Y EXACTAS

description

The cascade of molecular events leading to Human apolipoprotein A–I (apoA–I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants of apoA–I were described as inducing amyloidosis, but the mechanisms driving their aggregation and deposition are still unclear. We previously identified that the mutant Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen species from cultured RAW 264.7 murine macrophages, suggesting that part of the pathogenic pathway could elicit of an inflammatory signal. In this work we gained deep insight into this mechanism and determined that Gly26Arg induced a specific pro-inflammatory cascade involving activation of NF-κB and its translocation into the nucleus. These findings suggest that some but not all apoA–I natural variants might promote a pro-oxidant microenvironment which could in turn result in oxidative processing of the variants into a misfolded conformation. Fil: Ramella, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Andújar, Isabel. Fundación Hospital Universitario Dr. Peset; España. Universidad de Valencia; España Fil: Ríos, José Luis. Universidad de Valencia; España. Fundación Hospital Universitario Dr. Peset; España Fil: Rosu, Silvana Antonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Tricerri, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Schinella, Guillermo Raúl. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina

year	journal	country	edition	language
2018-12-01	Pathophysiology

https://doi.org/10.1016/j.pathophys.2018.08.002