Inhibition of Atm and Atr kinases affects embryo development and the DNA damage response in sterlet (Acipenser ruthenus)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F24%3A00616657" target="_blank" >RIV/60077344:_____/24:00616657 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60076658:12520/24:43908195

Výsledek na webu

<a href="https://doi.org/10.1016/j.aquaculture.2024.741146" target="_blank" >https://doi.org/10.1016/j.aquaculture.2024.741146</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.aquaculture.2024.741146" target="_blank" >10.1016/j.aquaculture.2024.741146</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Inhibition of Atm and Atr kinases affects embryo development and the DNA damage response in sterlet (Acipenser ruthenus)

Popis výsledku v původním jazyce

Embryo development is regulated by numerous interconnected pathways that direct cell fate, differentiation, and genetic stability. During development, these pathways can be altered by exogenous factors, such as pollutants, or endogenous factors, such as replication stress. Ataxia telangiectasia mutated (Atm) and ataxia telangiectasia and Rad3-related (Atr) kinases play critical roles in regulating the cell cycle, the DNA damage response (DDR), DNA repair, checkpoint activation, and apoptosis. In cells with damaged DNA, these kinases can slow the cell cycle to provide the necessary time and ability for DNA repair. In this study, we investigated the roles of Atm and Atr in embryo development and DDR in the sterlet ( Acipenser ruthenus ). Sterlets belong to the Acipenseridae family, one of the most threatened groups of species. Thus, understanding their genetics, biology, embryogenesis, and conservation is crucial. Furthermore, the sterlet is a significant aquaculture species that represents an intriguing model for studying polyploidy and genome plasticity. In our research, we examined the effects of chemical inhibition of Atm and Atr on sterlet embryo development in the absence and presence of the genotoxicant camptothecin (CPT). Our findings indicated that in the absence of genotoxic challenge, Atr autophosphorylation increases between 1 and 3 days post-fertilization (dpf) and decreases by 5 dpf, illustrating the involvement of Atr in the response to replication stress in rapidly differentiating tissues during the early stages of embryo development. Conversely, Atm inhibition was associated with a dosedependent reduction in embryo viability, highlighting its importance in normal embryo development. When sterlet embryos were exposed to CPT, both Atm and Atr were involved in DDR and the activation of apoptosis. Notably, when both kinases were inhibited simultaneously, the embryos lost their ability to induce apoptosis and mitigate DNA damage, resulting in 100% embryonic mortality. These results suggest that Atm and Atr have distinct functions during normal embryo development, but they can partially complement each other in DDR.

Název v anglickém jazyce

Inhibition of Atm and Atr kinases affects embryo development and the DNA damage response in sterlet (Acipenser ruthenus)

Popis výsledku anglicky

Embryo development is regulated by numerous interconnected pathways that direct cell fate, differentiation, and genetic stability. During development, these pathways can be altered by exogenous factors, such as pollutants, or endogenous factors, such as replication stress. Ataxia telangiectasia mutated (Atm) and ataxia telangiectasia and Rad3-related (Atr) kinases play critical roles in regulating the cell cycle, the DNA damage response (DDR), DNA repair, checkpoint activation, and apoptosis. In cells with damaged DNA, these kinases can slow the cell cycle to provide the necessary time and ability for DNA repair. In this study, we investigated the roles of Atm and Atr in embryo development and DDR in the sterlet ( Acipenser ruthenus ). Sterlets belong to the Acipenseridae family, one of the most threatened groups of species. Thus, understanding their genetics, biology, embryogenesis, and conservation is crucial. Furthermore, the sterlet is a significant aquaculture species that represents an intriguing model for studying polyploidy and genome plasticity. In our research, we examined the effects of chemical inhibition of Atm and Atr on sterlet embryo development in the absence and presence of the genotoxicant camptothecin (CPT). Our findings indicated that in the absence of genotoxic challenge, Atr autophosphorylation increases between 1 and 3 days post-fertilization (dpf) and decreases by 5 dpf, illustrating the involvement of Atr in the response to replication stress in rapidly differentiating tissues during the early stages of embryo development. Conversely, Atm inhibition was associated with a dosedependent reduction in embryo viability, highlighting its importance in normal embryo development. When sterlet embryos were exposed to CPT, both Atm and Atr were involved in DDR and the activation of apoptosis. Notably, when both kinases were inhibited simultaneously, the embryos lost their ability to induce apoptosis and mitigate DNA damage, resulting in 100% embryonic mortality. These results suggest that Atm and Atr have distinct functions during normal embryo development, but they can partially complement each other in DDR.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

40103 - Fishery

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Aquaculture

ISSN

0044-8486

e-ISSN

1873-5622

Svazek periodika

590

Číslo periodika v rámci svazku

May

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

741146

Kód UT WoS článku

001248743400001

EID výsledku v databázi Scopus

2-s2.0-85194553316