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

0533869 - BÚ 2021 RIV CH eng J - Journal Article
Čtveráčková, L. - Jančula, Daniel - Raška, J. - Babica, Pavel - Sovadinová, I.
Structure-dependent effects of phthalates on intercellular and intracellular communication in liver oval cells.
International Journal of Molecular Sciences. Roč. 21, č. 17 (2020), s. 1-21, č. článku 6069. E-ISSN 1422-0067
Institutional support: RVO:67985939
Keywords : gap junctional intercellular communication * mitogen-activated protein kinases Erk1/2 * phthalates
OECD category: Toxicology
Impact factor: 5.924, year: 2020
Method of publishing: Open access
https://doi.org/10.3390/ijms21176069

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.
Permanent Link: http://hdl.handle.net/11104/0313694