Generation of Advanced Glycation End-Products (AGEs) by glycoxidation mediated by copper and ROS in a human serum albumin (HSA) model peptide: reaction mechanism and damage in motor neuron cells

Autor(es)

Sandanielo Marques, Caroline Martins ^[1] ; Nunes, Emilene Arusievicz ^[1] ; Lago, Larissa ^[1] ; Pedron, Cibele Nicolaski ^[1] ; Manieri, Tania Maria ^[1] ; Sato, Roseli Hiromi ^[1] ; Oliveira Junior, Vani Xavier ^[1] ; Cerchiaro, Giselle ^[1]

Afiliação do(s) autor(es)

^[1] Fed Univ ABC, Ctr Nat Sci & Humanities, Ave Estados 5001, BR-09210580 Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS; v. 824, p. 42-51, DEC 2017.
• Citações Web of Science: 1

Resumo

Glucose, in the presence of reactive oxygen species (ROS), acts as an as an oxidative agent and drives deleterious processes in Diabetes Mellitus. We have studied the mechanism and the toxicological effects of glucose-dependent glycoxidation reactions driven by copper and ROS, using a model peptide based on the exposed sequence of Human Serum Albumin (HSA) and containing a lysine residue susceptible to copper complexation. The main products of these reactions are Advanced Glycation End-products (AGEs). Carboxymethyl lysine and pyrraline condensed on the model peptide, generating a Modified Peptide (MP). These products were isolated, purified, and tested on cultured motor neuron cells. We observed DNA damage, enhancement of membrane roughness, and formation of domes. We evaluated nuclear abnormalities by the cytokinesis-blocked micronucleus assay and we measured cytostatic and cytotoxic effects, chromosomal breakage, nuclear abnormalities, and cell death. AGEs formed by glycoxidation caused large micronucleus aberrations, apoptosis, and large-scale nuclear abnormalities, even at low concentrations. (AU)

• Processo FAPESP: 16/09652-9 - Danos a biomoléculas em sistema celular neuronal com desbalanço redox e metálico
• Beneficiário: Giselle Cerchiaro
• Modalidade de apoio: Auxílio à Pesquisa - Regular