Hypochlorous Acid Induces Caspase Dependent Apoptosis in &amp;lt;i&amp;gt;Saccharomyces cerevisiae&amp;lt;/i&amp;gt;

Nur Kaluç,Pinar B Thomas

doi:10.4236/jbm.2021.94004

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.

Highlights

Reactive oxygen species (ROS) are oxygen containing small, reactive chemical molecules
We examined the viability of wild type yeast cells exposed to different concentrations of Hypochlorous acid (HOCl) by the spotting assay: Cells were exposed to HOCl at 2720 μM, 1360 μM, 680 μM, 340 μM, 170 μM, 85 μM and 42,5 μM for 1, 5, 10, 15 and 30 minutes (Figure 1(A)). 2720 μM, 1360 μM, 680 μM, 340 μM and 170 μM HOCl led to cell death within 1 minute (Figure 1(B))
The viability of wild type cells exposed to 340 μM, 170 μM, or 85 μM HOCl for 5 minutes were quantified by the Colony Forming Unit (CFU) assay and compared to the untreated control (Figure 1(C))

Summary

Introduction

Reactive oxygen species (ROS) are oxygen containing small, reactive chemical molecules. They include both radicals and non-radical ROS. Radicals, including superoxide (O2−) and hydroxyl (OH), contain at least one unpaired electron, and are highly reactive. B. Thomas pochlorous acid (HOCl) and hydrogen peroxide (H2O2) are non-radical ROS which differ from radicals by having no unpaired electrons. ROS acts as cellular signaling molecules involved in several biological processes at physiologic concentrations [4]. ROS levels above physiologic concentrations cause damage to important cellular macromolecules, such as lipids, proteins and DNA, leading to cell death as well as several diseases, including atherosclerosis and Alzheimer’s disease [5] [6]

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