Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells

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Publikace nespadá pod Filozofickou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
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ČTVERÁČKOVÁ Lucie JANČULA Daniel RAŠKA Jan BABICA Pavel SOVADINOVÁ Iva

Rok publikování 2020
Druh Článek v odborném periodiku
Časopis / Zdroj International Journal of Molecular Sciences
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://www.mdpi.com/1422-0067/21/17/6069
Doi http://dx.doi.org/10.3390/ijms21176069
Klíčová slova gap junctional intercellular communication; gap junctions; hepatotoxicity; MAP-kinases Erk1; 2 activation; non-genomic mechanism; oval cells; phthalates; progenitor cells
Přiložené soubory
Popis 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.
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