Cargando…

P66Shc (Shc1) Zebrafish Mutant Line as a Platform for Testing Decreased Reactive Oxygen Species in Pathology

Reactive oxygen species (ROS) dysregulation exacerbates many pathologies but must remain within normal ranges to maintain cell function. Since ROS-mediated pathology and routine cell function are coupled, in vivo models evaluating low-ROS background effects on pathology are limited. Some models alte...

Descripción completa

Detalles Bibliográficos
Autores principales: Haslem, Landon, Hays, Jennifer M., Zhang, Xin A., Hays, Franklin A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694256/
https://www.ncbi.nlm.nih.gov/pubmed/36354784
http://dx.doi.org/10.3390/jcdd9110385
_version_ 1784837753979011072
author Haslem, Landon
Hays, Jennifer M.
Zhang, Xin A.
Hays, Franklin A.
author_facet Haslem, Landon
Hays, Jennifer M.
Zhang, Xin A.
Hays, Franklin A.
author_sort Haslem, Landon
collection PubMed
description Reactive oxygen species (ROS) dysregulation exacerbates many pathologies but must remain within normal ranges to maintain cell function. Since ROS-mediated pathology and routine cell function are coupled, in vivo models evaluating low-ROS background effects on pathology are limited. Some models alter enzymatic antioxidant expression/activity, while others involve small molecule antioxidant administration. These models cause non-specific ROS neutralization, decreasing both beneficial and detrimental ROS. This is detrimental in cardiovascular pathology, despite the negative effects excessive ROS has on these pathologies. Thus, current trends in ROS-mediated pathology have shifted toward selective inhibition of ROS producers that are dysregulated during pathological insults, such as p66Shc. In this study, we evaluated a zebrafish heterozygote p66Shc hypomorphic mutant line as a low-ROS myocardial infarction (MI) pathology model that mimics mammalian MI. Our findings suggest this zebrafish line does not have an associated negative phenotype, but has decreased body mass and tissue ROS levels that confer protection against ROS-mediated pathology. Therefore, this line may provide a low-ROS background leading to new insights into disease.
format Online
Article
Text
id pubmed-9694256
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96942562022-11-26 P66Shc (Shc1) Zebrafish Mutant Line as a Platform for Testing Decreased Reactive Oxygen Species in Pathology Haslem, Landon Hays, Jennifer M. Zhang, Xin A. Hays, Franklin A. J Cardiovasc Dev Dis Article Reactive oxygen species (ROS) dysregulation exacerbates many pathologies but must remain within normal ranges to maintain cell function. Since ROS-mediated pathology and routine cell function are coupled, in vivo models evaluating low-ROS background effects on pathology are limited. Some models alter enzymatic antioxidant expression/activity, while others involve small molecule antioxidant administration. These models cause non-specific ROS neutralization, decreasing both beneficial and detrimental ROS. This is detrimental in cardiovascular pathology, despite the negative effects excessive ROS has on these pathologies. Thus, current trends in ROS-mediated pathology have shifted toward selective inhibition of ROS producers that are dysregulated during pathological insults, such as p66Shc. In this study, we evaluated a zebrafish heterozygote p66Shc hypomorphic mutant line as a low-ROS myocardial infarction (MI) pathology model that mimics mammalian MI. Our findings suggest this zebrafish line does not have an associated negative phenotype, but has decreased body mass and tissue ROS levels that confer protection against ROS-mediated pathology. Therefore, this line may provide a low-ROS background leading to new insights into disease. MDPI 2022-11-09 /pmc/articles/PMC9694256/ /pubmed/36354784 http://dx.doi.org/10.3390/jcdd9110385 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Haslem, Landon
Hays, Jennifer M.
Zhang, Xin A.
Hays, Franklin A.
P66Shc (Shc1) Zebrafish Mutant Line as a Platform for Testing Decreased Reactive Oxygen Species in Pathology
title P66Shc (Shc1) Zebrafish Mutant Line as a Platform for Testing Decreased Reactive Oxygen Species in Pathology
title_full P66Shc (Shc1) Zebrafish Mutant Line as a Platform for Testing Decreased Reactive Oxygen Species in Pathology
title_fullStr P66Shc (Shc1) Zebrafish Mutant Line as a Platform for Testing Decreased Reactive Oxygen Species in Pathology
title_full_unstemmed P66Shc (Shc1) Zebrafish Mutant Line as a Platform for Testing Decreased Reactive Oxygen Species in Pathology
title_short P66Shc (Shc1) Zebrafish Mutant Line as a Platform for Testing Decreased Reactive Oxygen Species in Pathology
title_sort p66shc (shc1) zebrafish mutant line as a platform for testing decreased reactive oxygen species in pathology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694256/
https://www.ncbi.nlm.nih.gov/pubmed/36354784
http://dx.doi.org/10.3390/jcdd9110385
work_keys_str_mv AT haslemlandon p66shcshc1zebrafishmutantlineasaplatformfortestingdecreasedreactiveoxygenspeciesinpathology
AT haysjenniferm p66shcshc1zebrafishmutantlineasaplatformfortestingdecreasedreactiveoxygenspeciesinpathology
AT zhangxina p66shcshc1zebrafishmutantlineasaplatformfortestingdecreasedreactiveoxygenspeciesinpathology
AT haysfranklina p66shcshc1zebrafishmutantlineasaplatformfortestingdecreasedreactiveoxygenspeciesinpathology