Metal-based superoxide dismutase and catalase mimics reduce oxidative stress biomarkers and extend life span of Saccharomyces cerevisiae

Biochem J. 2017 Jan 15;474(2):301-315. doi: 10.1042/BCJ20160480. Epub 2016 Nov 15.

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)2 and 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.

Keywords: SOD and CAT mimics; Saccharomyces cerevisiae; chronological aging; lipid droplets; metal homeostasis.

MeSH terms

  • Biomarkers / metabolism
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / metabolism
  • Biomimetic Materials / pharmacology*
  • Catalase / metabolism*
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology*
  • Copper / chemistry
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / pharmacology
  • Iron / chemistry
  • Lipid Droplets / drug effects
  • Manganese / chemistry
  • Microbial Viability / drug effects
  • Oxidation-Reduction
  • Oxidative Stress
  • Pyridines / chemical synthesis
  • Pyridines / metabolism
  • Pyridines / pharmacology*
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / metabolism
  • Superoxide Dismutase / deficiency*

Substances

  • Biomarkers
  • Coordination Complexes
  • Pyridines
  • Saccharomyces cerevisiae Proteins
  • Manganese
  • Copper
  • Hydrogen Peroxide
  • Iron
  • Catalase
  • Superoxide Dismutase