S-Adenosylmethionine regulates connexins sub-types expressed by hepatocytes
| Autor: | María L. Martínez-Chantar, Anne E. Warner, Shelly C. Lu, S. Yamaji, Marta Varela-Rey, Anna Droggiti |
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| Rok vydání: | 2011 |
| Předmět: |
S-Adenosylmethionine
Histology Cellular differentiation Connexin Biology Article Connexins Pathology and Forensic Medicine Mice chemistry.chemical_compound MG132 medicine Animals Receptor Cells Cultured beta Catenin Tissue homeostasis Mice Knockout Regulation of gene expression Thionucleosides Deoxyadenosines Gap Junctions Cell Differentiation Cell Biology General Medicine Molecular biology Cell biology medicine.anatomical_structure Gene Expression Regulation chemistry Hepatocyte Hepatocytes Proteasome inhibitor medicine.drug |
| Zdroj: | European Journal of Cell Biology. 90:312-322 |
| ISSN: | 0171-9335 |
| DOI: | 10.1016/j.ejcb.2010.09.007 |
| Popis: | Intercellular communication via GAP Junctions plays an important role in tissue homeostasis, apoptosis, carcinogenesis, cell proliferation and differentiation. Hepatocyte connexins (Cx) 26 and 32 levels are decreased during the de-differentiation process of primary hepatocytes in culture, a situation that is also characterized by a decrease in S-Adenosylmethionine (SAMe) levels. In this current study, we show that SAMe supplementation in cultured hepatocytes every 12h, leads to an up-regulation of Cx26 and 32 mRNA and protein levels and blocks culture-induced Cx43 expression, although it failed to increase Cx26 and 32 membrane localization and GAP junction intracellular communication. SAMe reduced nuclear β-catenin accumulation, which is known to stimulate the TCF/LEF-dependent gene transcription of Cx43. Moreover SAMe-induced reduction in Cx43 and β-catenin was prevented by the proteasome inhibitor MG132, and was not mediated by GSK3 activity. SAMe, and its metabolite 5'-methylthioadenosine (MTA) increased Cx26 mRNA in a process partially mediated by Adenosine A(2A) receptors but independent of PKA. Finally livers from MAT1A knockout mice, characterized by low hepatic SAMe levels, express higher Cx43 and lower Cx26 and 32 protein levels than control mice. These results suggest that SAMe maintains a characteristic expression pattern of the different Cxs in hepatocytes by differentially regulating their levels. |
| Databáze: | OpenAIRE |
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