A Stochastic Characterization of Hydrogen Peroxide-Induced Regulated Cell Death in Microcystis aeruginosa

Regulated cell death (RCD) encompasses the activation of cellular pathways that initiate and execute a self-dismissal process. RCD occur over a range of stressors doses that overcome pro-survival cellular pathways, while higher doses cause excessive damage leading to passive accidental cell death (A...

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Autores principales: Giannuzzi, Leda, Lombardo, Tomás, Juárez, Iván, Aguilera, Anabella, Blanco, Guillermo A.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2021
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/134539
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id I19-R120-10915-134539
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Química
cyanobacteria
Microcystis
cell death
regulated cell death
binary logistic function
EC50
spellingShingle Ciencias Exactas
Química
cyanobacteria
Microcystis
cell death
regulated cell death
binary logistic function
EC50
Giannuzzi, Leda
Lombardo, Tomás
Juárez, Iván
Aguilera, Anabella
Blanco, Guillermo A.
A Stochastic Characterization of Hydrogen Peroxide-Induced Regulated Cell Death in Microcystis aeruginosa
topic_facet Ciencias Exactas
Química
cyanobacteria
Microcystis
cell death
regulated cell death
binary logistic function
EC50
description Regulated cell death (RCD) encompasses the activation of cellular pathways that initiate and execute a self-dismissal process. RCD occur over a range of stressors doses that overcome pro-survival cellular pathways, while higher doses cause excessive damage leading to passive accidental cell death (ACD). Hydrogen peroxide (HP) has been proposed as a potential tool to control harmful cyanobacterial blooms, given its capacity to remove cyanobacterial cells and oxidize cyanotoxins. HP is a source of hydroxyl radicals and is expected to induce RCD only within a limited range of concentrations. This property makes this compound very useful to better understand stress-driven RCD. In this work, we analyzed cell death in microcystin-producing <i>Microcystis aeruginosa</i> by means of a stochastic dose response model using a wide range of HP concentrations (0, 0.29, 1.76, 3.67, 7.35, 14.70, and 29.5 mM). We used flow cytometry and unsupervised classification to study cell viability and characterize transitional cell death phenotypes after exposing cells to HP for 48 and 72 h. Non-linear regression was used to fit experimental data to a logistic cumulative distribution function (cdf) and calculate the half maximal effective concentration (EC₅₀). The EC₅₀ of <i>M. aeruginosa</i> exposed to HP were 3.77 ± 0.26 mM and 4.26 ± 0.22 mM at 48 and 72 h, respectively. The derivative of cdf (probability density function; pdf) provided theoretical and practical demonstration that EC₅₀ is the minimal dose required to cause RCD in 50% of cells, therefore maximizing the probability of RCD occurrence. 1.76 mM HP lead to an antioxidant stress response characterized by increased reactive oxygen species (ROS) levels and HP decomposition activity. The exposure of 3.67 mM HP induced a dose-related transition in cell death phenotype, and produced several morphological changes (a less dense stroma, distortion of the cell membrane, partial disintegration of thylakoids, extensive cytoplasmic vacuolation and highly condensed chromatin). The EC₅₀ and the stochastic cdf and pdf together with the multidimensional transitional phenotypic analysis of single cells contribute to further characterize cell death pathways in cyanobacteria.
format Articulo
Articulo
author Giannuzzi, Leda
Lombardo, Tomás
Juárez, Iván
Aguilera, Anabella
Blanco, Guillermo A.
author_facet Giannuzzi, Leda
Lombardo, Tomás
Juárez, Iván
Aguilera, Anabella
Blanco, Guillermo A.
author_sort Giannuzzi, Leda
title A Stochastic Characterization of Hydrogen Peroxide-Induced Regulated Cell Death in Microcystis aeruginosa
title_short A Stochastic Characterization of Hydrogen Peroxide-Induced Regulated Cell Death in Microcystis aeruginosa
title_full A Stochastic Characterization of Hydrogen Peroxide-Induced Regulated Cell Death in Microcystis aeruginosa
title_fullStr A Stochastic Characterization of Hydrogen Peroxide-Induced Regulated Cell Death in Microcystis aeruginosa
title_full_unstemmed A Stochastic Characterization of Hydrogen Peroxide-Induced Regulated Cell Death in Microcystis aeruginosa
title_sort stochastic characterization of hydrogen peroxide-induced regulated cell death in microcystis aeruginosa
publishDate 2021
url http://sedici.unlp.edu.ar/handle/10915/134539
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