Ceramide/protein phosphatase 2A axis is engaged in gap junction impairment elicited by PCB153 in liver stem-like progenitor cells
| Autor: | Federica Pierucci, Fabio Francini, Elena Lenci, Maria Chiara Iachini, Catia Vicenti, Elisabetta Meacci, Rachele Garella, Alessia Frati, Maria Caterina Baccari, Roberta Squecco, Maria Martinesi, Eglantina Idrizaj |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Ceramide Clinical Biochemistry Connexin Cell Communication Ceramides Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Protein Phosphatase 2 Progenitor cell Molecular Biology Cells Cultured Sphingolipids Sphingosine Stem Cells Gap junction Gap Junctions Cell Biology General Medicine Protein phosphatase 2 Polychlorinated Biphenyls Sphingolipid Rats Cell biology Protein Phosphatase 2A 030104 developmental biology Liver chemistry 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) Environmental pollutant PCB153 Signal Transduction Toxicant |
| Zdroj: | Molecular and Cellular Biochemistry |
| ISSN: | 1573-4919 0300-8177 |
| DOI: | 10.1007/s11010-021-04135-z |
| Popis: | The widespread environmental pollutant 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) is a non-dioxin-like toxicant. It is a potential carcinogen compound able to induce gap junction (GJ) intercellular communication impairment, probably the first non-genomic event leading to tumor promotion. Although PCBs have been known for many years, the molecular mode of PCB153 action is still unclear. Recent studies from our research group have shown that the toxicant elicits a transient modulation of connexin (Cx) 43-formed GJs in hepatic stem-like WB-F344 cells involving sphingosine 1-phosphate (S1P) path. Taking into account that other strictly related bioactive sphingolipids, such as ceramide (Cer), may have different effects from S1P, here we aim to clarify the signaling paths engaged by PCB153 in the control of GJs, focusing primarily on the role of Cer. Accordingly, we have achieved a combined biomolecular and electrophysiological analysis of GJs in cultured WB-F344 cells treated with PCB153 at different time points. We have found that the toxicant elicited a time-dependent regulation of GJs formed by different Cx isoforms, through a transient modulation of Cer/Cer kinase (CerK) axis and, in turn, of protein phosphatase 2A (PP2A). Our new findings demonstrate the existence of a specific molecular mechanism downstream to Cer, which distinctly affects the voltage-dependent and -independent GJs in liver stem-like cells, and open new opportunities for the identification of additional potential targets of these environmental toxicants. Supplementary Information The online version contains supplementary material available at 10.1007/s11010-021-04135-z. |
| Databáze: | OpenAIRE |
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