title: Metal-based superoxide dismutase and catalase mimics reduce oxidative stress biomarkers and extend life span of Saccharomyces cerevisiae.
abstract: Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl2]NO3, [Cu(HPClNOL)(CH3CN)](ClO4)2and Mn(HPClNOL)(Cl)2}, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's.
authors.affiliation: Laboratório de Citotoxicidade e Genotoxicidade, Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Thales de P
authors.initials: TP
authors.lastname: Ribeiro
authors.affiliation: Centro de Desenvolvimento Tecnológico em Saúde, CDTS Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Fernanda L
authors.initials: FL
authors.lastname: Fonseca
authors.affiliation: Laboratório de Citotoxicidade e Genotoxicidade, Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Mariana D C
authors.initials: MD
authors.lastname: de Carvalho
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Rodrigo M da C
authors.initials: RM
authors.lastname: Godinho
authors.affiliation: Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO), Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Fernando Pereira
authors.initials: FP
authors.lastname: de Almeida
authors.affiliation: Laboratório de Espectrometria Atômica (LABSPECTRO), Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Tatiana D
authors.initials: TD
authors.lastname: Saint'Pierre
authors.affiliation: Laboratório de Síntese Orgânica e Química de Coordenação Aplicada a Sistemas Biológicos (LABSO-BIO), Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Nicolás A
authors.initials: NA
authors.lastname: Rey
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil.
authors.forename: Christiane
authors.initials: C
authors.lastname: Fernandes
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Horn
authors.affiliation: Laboratório de Citotoxicidade e Genotoxicidade, Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil marcosdp@iq.ufrj.br.
authors.forename: Marcos D
authors.initials: MD
authors.lastname: Pereira
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007501:Iron / Q000737:chemistry; D066292:Lipid Droplets / Q000187:drug effects; D008345:Manganese / Q000737:chemistry; D050296:Microbial Viability / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000172:deficiency*
chemical_list: D015415:Biomarkers; D056831:Coordination Complexes; D011725:Pyridines; D029701:Saccharomyces cerevisiae Proteins; D008345:Manganese; D003300:Copper; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase
keywords: SOD and CAT mimics; Saccharomyces cerevisiae; chronological aging; lipid droplets; metal homeostasis