2020
Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells
ČTVERÁČKOVÁ, Lucie; Daniel JANČULA; Jan RAŠKA; Pavel BABICA; Iva SOVADINOVÁ et al.Základní údaje
Originální název
Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells
Autoři
Vydání
International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2020, 1422-0067
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10608 Biochemistry and molecular biology
Stát vydavatele
Švýcarsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Označené pro přenos do RIV
Ano
Kód RIV
RIV/00216224:14310/20:00114568
Organizační jednotka
Přírodovědecká fakulta
UT WoS
EID Scopus
Klíčová slova anglicky
gap junctional intercellular communication; gap junctions; hepatotoxicity; MAP-kinases Erk1; 2 activation; non-genomic mechanism; oval cells; phthalates; progenitor cells
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 2. 6. 2025 21:50, Mgr. Michaela Hylsová, Ph.D.
Anotace
V originále
Humans are exposed to phthalates released from plastics, cosmetics, or food on a daily basis. Phthalates have low acute liver toxicity, but their chronic exposures could induce molecular and cellular effects linked to adverse health outcomes, such as liver tumor promotion or chronic liver diseases. The alternation of gap junctional intercellular communication (GJIC) and MAPK-Erk1/2 pathways in liver progenitor or oval cells can disrupt liver tissue homeostatic mechanisms and affect the development and severity of these adverse outcomes. Our study with 20 different phthalates revealed their structurally dependent effects on liver GJIC and MAPK-Erk1/2 signaling in rat liver WB-F344 cell line with characteristics of liver 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.
Návaznosti
| EF17_043/0009632, projekt VaV |
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| GJ16-10775Y, projekt VaV |
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| 857560, interní kód MU (Kód CEP: EF17_043/0009632) |
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| 90121, velká výzkumná infrastruktura |
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