Structure-dependent effects of phthalates on intercellular and intracellular communication in liver oval cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985939%3A_____%2F20%3A00533869" target="_blank" >RIV/67985939:_____/20:00533869 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.3390/ijms21176069" target="_blank" >https://doi.org/10.3390/ijms21176069</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21176069" target="_blank" >10.3390/ijms21176069</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structure-dependent effects of phthalates on intercellular and intracellular communication in liver oval cells

Popis výsledku v původním jazyce

This study with 20 different phthalates identified their structurally dependent effects on inhibition of gap junctional intercellular communication and activation of MAPK-Erk1/2 signaling in rat oval cells. The phthalates with a medium-length side chain (3–6 C) were the most potent dysregulators of GJIC and activators of MAPK-Erk1/2. The effects occurred rapidly, suggesting the activation of non-genomic (non-transcriptional) mechanisms directly by the parental compounds. Short-chain phthalates (1–2 C) did not dysregulate GJIC even after longer exposures and did not activate MAPK-Erk1/2. Longer chain (≥7 C) phthalates, such as DEHP or DINP, moderately activated MAPK-Erk1/2, but inhibited GJIC only after prolonged exposures (>12 h), suggesting that GJIC dysregulation occurs via genomic mechanisms, or (bio)transformation. Overall, medium-chain phthalates rapidly affected the key tissue homeostatic mechanisms in the liver oval cell population via non-genomic pathways, which might contribute to the development of chronic liver toxicity and diseases.

Název v anglickém jazyce

Structure-dependent effects of phthalates on intercellular and intracellular communication in liver oval cells

Popis výsledku anglicky

This study with 20 different phthalates identified their structurally dependent effects on inhibition of gap junctional intercellular communication and activation of MAPK-Erk1/2 signaling in rat oval cells. The phthalates with a medium-length side chain (3–6 C) were the most potent dysregulators of GJIC and activators of MAPK-Erk1/2. The effects occurred rapidly, suggesting the activation of non-genomic (non-transcriptional) mechanisms directly by the parental compounds. Short-chain phthalates (1–2 C) did not dysregulate GJIC even after longer exposures and did not activate MAPK-Erk1/2. Longer chain (≥7 C) phthalates, such as DEHP or DINP, moderately activated MAPK-Erk1/2, but inhibited GJIC only after prolonged exposures (>12 h), suggesting that GJIC dysregulation occurs via genomic mechanisms, or (bio)transformation. Overall, medium-chain phthalates rapidly affected the key tissue homeostatic mechanisms in the liver oval cell population via non-genomic pathways, which might contribute to the development of chronic liver toxicity and diseases.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

21

Strana od-do

1-21

Kód UT WoS článku

000569736100001

EID výsledku v databázi Scopus

2-s2.0-85089924980