No abstract

Cancer cells are defined by abnormal and unrestricted mitotic divisions, therefore targeting mitosis is a useful strategy for cancer treatment. Two groups of drugs that are most successfully used in the treatment of several types of cancer, taxanes and vinca alkaloids, exhibit their anti-tumor effects by causing a mitotic arrest. However, not much is known about whether being arrested in mitosis affects the sensitivity of cells to tumor-related stresses, such as oxidative and osmotic stresses. In this study, we investigated whether mitosis affects the sensitivity of Saccharomyces cerevisiae cells to H2O2-induced oxidative stress and sorbitol-induced osmotic stress. Mitotic and G1-arrests were induced by nocodazole and alpha factor, respectively. The effects of nocodazole or alpha factor treatments on the sensitivity of wild type (WT) and MAD3 deletion (mad3Δ) strains to oxidative stress and osmotic stress were evaluated by the spotting and coloni forming unit (cfu) assays as well as detection of reactive oxygen species (ROS) production. Data were analyzed using Student's t-test and expressed as standard deviation (std), p<0.05 was considered significant. Our data indicate that mitosis significantly increases resistance to oxidative stress, however it does not have any significant effect on the osmotic stress resistance in yeast.

Slx5, a subunit of a SUMO-targeted ubiquitin ligase (STUbL) in yeast, has been implicated in maintenance of genomic stability. SUMOylation is an important post-translational modification involved in the regulation of several important cellular processes and cellular response to various environmental stressors. Oxidative stress occurs when production of reactive oxygen species (ROS) exceeds the antioxidant defense capacity of the cell. Elevated ROS levels cause oxidative damage to important cellular macromolecules such as DNA, lipids and proteins, which is associated with several diseases. Herein, we investigated the role of Slx5 in oxidative stress tolerance in Saccharomyces cerevisiae. We show that deletion of SLX5 increases survival of yeast cells in response to H2O2-induced oxidative stress in a cell cycle independent manner. Accumulation of intracellular ROS as well as DNA and lipid damages were reduced; expressions of antioxidant defense mechanism related genes were increased in slx5Δ cells compared to wild type (WT) under oxidative stress. We also show that slx5Δ cells have increased intracellular ROS levels and oxidative damage to DNA and lipids compared to WT in the absence of oxidative stress. Thus, our data together suggest that an adaptive stress induced by SLX5 deletion increases tolerance to oxidative stress in slx5∆ cells.

No abstract

Hypochlorous acid (HOCl) is a strong oxidant produced by activated neutrophils via the myeloperoxidase (MPO) enzyme in order to fight against infections. Because of their antimicrobial and antiviral properties, stabilized HOCl solutions were produced to be used as a disinfectant and became a recommended disinfectant against COVID-19 by the US Environmental Protection Agency. Aberrant MPO enzyme activity results in abundant HOCl production which is related to the development and/or progression of several diseases including atherosclerosis, cardiovascular and neurodegenerative diseases. Previous studies investigating the effect of HOCl on the mode of cell death in different cell types reported that HOCl induces both apoptosis and necrosis depending on its concentration. However, the data on the apoptotic pathway triggered by HOCl is controversial. In this study, we investigated the mode of cell death induced by different concentrations of HOCl in Saccharomyces cerevisiae. Our data revealed that HOCl leads to cell death within 1 minute at 170 µM and above. At 340 µM, HOCl causes a rapid necrosis, while 170 µM HOCl leads to apoptosis. HOCl-induced apoptosis is mostly caspase dependent and Aif1 doesn't have a significant role.