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)Cl]NO, [Cu(HPClNOL)(CHCN)](ClO) and Mn(HPClNOL)(Cl)}, 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.

Enhanced corrosion resistance of zinc-containing nanowires-modified titanium surface under exposure to oxidizing microenvironment

“…Catalase (CAT), an enzyme found mainly in peroxisomes, can degrade hydrogen peroxide to water and oxygen and thus exert vital roles in resistance to oxidative cell injury [48]. Meanwhile, CAT inhibits the release of hydrogen peroxide into extracellular matrix and reduce oxidative stress reaction on the metal surfaces [49]. Here, Ti-NW-Zn samples obviously increased CAT expression in attached macrophages with more than fourfolds change compared to the other three surfaces (Fig.…”

Superoxide Dismutase Administration: A Review of Proposed Human Uses

“…S. cerevisiae is a suitable eukaryotic model for aging as it recapitulates the susceptibility of human cells to the proteotoxicity of α-synuclein, amyloid-β, the poliQ trait of Huntington's and mutant forms of SOD1 [180]. This model has been used to investigate the possible use of SOD mimetics as therapeutic agents against aging-related diseases, such as Parkinson's and Alzheimer's, and promising results have been obtained [286].…”

“…Compared to the salen-manganese complexes, the metal-based compounds have not been observed to affect the capacity of cells to synthesize neutral lipids and to compartmentalize them into lipid droplets. Cell-membrane integrity is thus maintained, hinting at possible higher efficacy against aging [286]. However, further studies that explore the real mechanism of action of these compounds must be performed to support this hypothesis.…”

Effect of Nitrosative Stress on the S-Nitroso-Proteome of Paracoccidioides brasiliensis

“…It was demonstrated in Candida albicans that the response to nitrosative stress activates genes that regulate the expression of oxidative stress, such as catalase (Cat1), glutathione, NADPH oxidoreductase and dehydrogenase (Brown et al, 2014) elements that were identified on the proteomic analysis (Supplementary Table S1). In biological systems, cells have an antioxidant repertoire essential to ROS protection, which activates several effector molecules (Ribeiro et al, 2017).…”