Hydrogen peroxide induced cell death: One or two modes of action?

Uhl, Lionel; Gerstel, Audrey; Chabalier, Maïalène; Dukan, Sam

doi:10.1016/j.heliyon.2015.e00049

Cited by 45 publications

(34 citation statements)

References 35 publications

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“…Using published rate constants, we propose here some simplifications and approximations of the system achieved by neglecting the kinetically non-significant reaction. HO • was studied in a previous article ([ 3 ]).…”

Section: Methodsmentioning

confidence: 99%

“…In order to better understand ROS dynamic within cells, we recently developed a mathematical model ([ 3 ]) for predicting reactive oxygen species (ROS) concentration and macromolecules oxidation invivo . This first study principally focuses on HO • dynamic and its consequence on DNA whereas the current study will mainly focus on H 2 O 2 dynamic.…”

Section: Introductionmentioning

confidence: 99%

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Hydrogen Peroxide Induced Cell Death: The Major Defences Relative Roles and Consequences in E. coli

Uhl

Dukan

2016

PLoS ONE

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We recently developed a mathematical model for predicting reactive oxygen species (ROS) concentration and macromolecules oxidation in vivo. We constructed such a model using Escherichia coli as a model organism and a set of ordinary differential equations. In order to evaluate the major defences relative roles against hydrogen peroxide (H2 O2), we investigated the relative contributions of the various reactions to the dynamic system and searched for approximate analytical solutions for the explicit expression of changes in H2 O2 internal or external concentrations. Although the key actors in cell defence are enzymes and membrane, a detailed analysis shows that their involvement depends on the H2 O2 concentration level. Actually, the impact of the membrane upon the H2 O2 stress felt by the cell is greater when micromolar H2 O2 is present (9-fold less H2 O2 in the cell than out of the cell) than when millimolar H2 O2 is present (about 2-fold less H2 O2 in the cell than out of the cell). The ratio between maximal external H2 O2 and internal H2 O2 concentration also changes, reducing from 8 to 2 while external H2 O2 concentration increases from micromolar to millimolar. This non-linear behaviour mainly occurs because of the switch in the predominant scavenger from Ahp (Alkyl Hydroperoxide Reductase) to Cat (catalase). The phenomenon changes the internal H2 O2 maximal concentration, which surprisingly does not depend on cell density. The external H2 O2 half-life and the cumulative internal H2 O2 exposure do depend upon cell density. Based on these analyses and in order to introduce a concept of dose response relationship for H2 O2-induced cell death, we developed the concepts of “maximal internal H2 O2 concentration” and “cumulative internal H2 O2 concentration” (e.g. the total amount of H2 O2). We predict that cumulative internal H2 O2 concentration is responsible for the H2 O2-mediated death of bacterial cells.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hydrogen Peroxide Induced Cell Death: The Major Defences Relative Roles and Consequences in E. coli

Uhl

Dukan

2016

PLoS ONE

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“…Surprisingly, the exact mechanism(s) by which H 2 O 2 leads to cell death remain poorly understood (Whittemore et al , ; Day et al , ; Uhl et al , ). The mediocre reactivity of H 2 O 2 with most biological molecules argues against direct oxidation of cellular biomolecules being a principal driver of cell death, at least at physiologically relevant H 2 O 2 concentrations (Winterbourn & Metodiewa, ; Stone, ; Winterbourn, ).…”

Section: Introductionmentioning

confidence: 99%

“…Presumably therefore, cells strive to tightly regulate H 2 O 2 to permit sufficiently large fluctuations in H 2 O 2 concentration for signaling purposes, while simultaneously preventing accumulation of H 2 O 2 to toxic levels. Surprisingly, the exact mechanism(s) by which H 2 O 2 leads to cell death remain poorly understood (Whittemore et al, 1995;Day et al, 2012;Uhl et al, 2015). The mediocre reactivity of H 2 O 2 with most biological molecules argues against direct oxidation of cellular biomolecules being a principal driver of cell death, at least at physiologically relevant H 2 O 2 concentrations (Winterbourn & Metodiewa, 1999;Stone, 2004;Winterbourn, 2008).…”

Section: Introductionmentioning

confidence: 99%

Hyperoxidation of mitochondrial peroxiredoxin limits H ₂ O ₂ ‐induced cell death in yeast

et al. 2019

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Hydrogen peroxide (H2O2) plays important roles in cellular signaling, yet nonetheless is toxic at higher concentrations. Surprisingly, the mechanism(s) of cellular H2O2 toxicity remain poorly understood. Here, we reveal an important role for mitochondrial 1‐Cys peroxiredoxin from budding yeast, Prx1, in regulating H2O2‐induced cell death. We show that Prx1 efficiently transfers oxidative equivalents from H2O2 to the mitochondrial glutathione pool. Deletion of PRX1 abrogates glutathione oxidation and leads to a cytosolic adaptive response involving upregulation of the catalase, Ctt1. Both of these effects contribute to improved cell viability following an acute H2O2 challenge. By replacing PRX1 with natural and engineered peroxiredoxin variants, we could predictably induce widely differing matrix glutathione responses to H2O2. Therefore, we demonstrated a key role for matrix glutathione oxidation in driving H2O2‐induced cell death. Finally, we reveal that hyperoxidation of Prx1 serves as a switch‐off mechanism to limit oxidation of matrix glutathione at high H2O2 concentrations. This enables yeast cells to strike a fine balance between H2O2 removal and limitation of matrix glutathione oxidation.

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“…CAT and GPx enzymes act with the same purpose, to prevent the hydrogen peroxide accumulation. Such integrated action is of great importance, since this reactive species through the reactions of Fenton and Haber-Weiss, with the participation of iron and copper metals, culminates in the generation of OH • radical against which there is no enzyme system defense [13,14].…”

Section: Antioxidant Defense Systemmentioning

confidence: 99%

Oxidative Stress and Disease

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Typically in aerobic metabolism, organic compounds such as nucleic acids, proteins and lipids can undergo structural damage by oxidative reactions. This damage caused by reactive oxygen/nitrogen species has been recognized as "oxidative stress". Despite the biological systems present efficient enzymatic and nonenzymatic antioxidant systems, oxidative stress indicates a pro-oxidant/antioxidant imbalance in favor of excessive generation of free radicals or decrease in the removal rate. Various diseases such as cancer, diabetes, cardiovascular diseases and neurodegenerative clearly exemplify the chronic oxidative stress. Therefore, it is important to consider that at low and moderate ROS levels, it can, for example, act as signaling molecules that support cell proliferation and differentiation and activate survival pathways in response to stress. Correlations between oxidative stress and disease should be carefully investigated in order to understand whether oxidative stress actually increases susceptibility to a particular disease or opposite.

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Hydrogen peroxide induced cell death: One or two modes of action?

Cited by 45 publications

References 35 publications

Hydrogen Peroxide Induced Cell Death: The Major Defences Relative Roles and Consequences in E. coli

Hydrogen Peroxide Induced Cell Death: The Major Defences Relative Roles and Consequences in E. coli

Hyperoxidation of mitochondrial peroxiredoxin limits H ₂ O ₂ ‐induced cell death in yeast

Oxidative Stress and Disease

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Hydrogen peroxide induced cell death: One or two modes of action?

Cited by 45 publications

References 35 publications

Hydrogen Peroxide Induced Cell Death: The Major Defences Relative Roles and Consequences in E. coli

Hydrogen Peroxide Induced Cell Death: The Major Defences Relative Roles and Consequences in E. coli

Hyperoxidation of mitochondrial peroxiredoxin limits H 2 O 2 ‐induced cell death in yeast

Oxidative Stress and Disease

Contact Info

Product

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Hyperoxidation of mitochondrial peroxiredoxin limits H ₂ O ₂ ‐induced cell death in yeast