Mitigating methylglyoxal-induced glycation stress: the protective role of iron, copper, and manganese coordination compounds in Saccharomyces cerevisiae

Biochem J. 2024 Dec 4;481(23):1771-1786. doi: 10.1042/BCJ20240390.

Abstract

Glycation-induced stress (G-iS) is a physiological phenomenon that leads to the formation of advanced glycation end-products, triggering detrimental effects such as oxidative stress, inflammation, and damage to intracellular structures, tissues, and organs. This process is particularly relevant because it has been associated with various human pathologies, including cancer, neurodegenerative diseases, and diabetes. As therapeutic alternatives, coordination compounds with antioxidant activity show promising potential due to their versatility in attenuating oxidative stress and inflammation. Herein, we investigated the antioxidant-related protective potential of a series of complexes: [Cu(II)(BMPA)Cl2] (1), [Fe(III)(BMPA)Cl3] (2), and [Cl(BMPA)MnII-(μ-Cl)2-MnII(BMPA)-(μ-Cl)- MnII(BMPA)(Cl)2]•5H2O (3), all synthesized with the ligand bis-(2-pyridylmethyl)amine (BMPA) in Saccharomyces cerevisiae exposed to G-iS caused by methylglyoxal (MG). Pre- treatment with complexes 1-3 proved highly effective, increasing yeast tolerance to G-iS and attenuating mitochondrial dysfunction. This observed phenotype appears to result from a reduction in intracellular oxidation, lipid peroxidation levels, and glycation. Additionally, an increase in the activity of the antioxidant enzymes superoxide dismutase and catalase was observed following treatment with complexes 1-3. Notably, although complexes 1-3 provided significant protection against oxidative stress induced by H2O2 and menadione, their protective role was more effective against MG-induced glycation stress. Our results indicate that these complexes possess both antiglycation and antioxidant properties, warranting further investigation as potential interventions for mitigating glycation and oxidative stress-related pathologies.

Keywords: Saccharomyces cerevisiae; advanced glycation end products; antiglycation activity; antioxidant response elements; methylglyoxal; oxidative stress.

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Copper* / chemistry
  • Copper* / metabolism
  • Glycation End Products, Advanced / metabolism
  • Glycosylation / drug effects
  • Iron* / metabolism
  • Manganese* / chemistry
  • Manganese* / metabolism
  • Oxidative Stress* / drug effects
  • Pyruvaldehyde* / metabolism
  • Saccharomyces cerevisiae* / drug effects
  • Saccharomyces cerevisiae* / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • Pyruvaldehyde
  • Copper
  • Manganese
  • Iron
  • Coordination Complexes
  • Antioxidants
  • Glycation End Products, Advanced
  • Superoxide Dismutase