|
|||||
|
|
Striatal adenosine A2A receptor expression is controlled by S-adenosyl-L-methionine-mediated methylation |
|
| Authors: | Izaskun Villar-Menéndez Fabiana Nuñez Sara Díaz-Sánchez José Luis Albasanz Jaume Taura Víctor Fernández-Dueñas Isidre Ferrer Mairena Martín Francisco Ciruela Marta Barrachina |
| Affiliation: | 1. Institute of Neuropathology, Bellvitge Biomedical Research Institute (IDIBELL), Bellvitge University Hospital-ICS, Av. Gran Via de L’Hospitalet 199, L’Hospitalet de Llobregat, 08908, Spain 2. Unitat de Farmacologia, Departament de Patologia i Terapèutica Experimental, IDIBELL, Universitat de Barcelona, L’Hospitalet de Llobregat, Spain 3. Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Ciencias y Tecnologías Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha, Ciudad Real, Spain 4. Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Medicina de Ciudad Real, CRIB, Universidad de Castilla-La Mancha, Ciudad Real, Spain 5. Departament de Patologia i Terapèutica Experimental, Universitat de Barcelona, L’Hospitalet de Llobregat, Spain 6. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain 7. Unitat de Farmacologia, Departament de Patologia i Terapèutica Experimental, IDIBELL, Universitat de Barcelona, c/Feixa Llarga s/n, 08907, L’Hospitalet de Llobregat, Spain |
| Abstract: | Adenosine A2A receptor (A2AR) is a G protein-coupled receptor enriched in the striatum for which an increased expression has been demonstrated in certain neurological diseases. Interestingly, previous in vitro studies demonstrated that A2AR expression levels are reduced after treatment with S-adenosyl-L-methionine (SAM), a methyl donor molecule involved in the methylation of important biological structures such as DNA, proteins, and lipids. However, the in vivo effects of SAM treatment on A2AR expression are still obscure. Here, we demonstrated that 2 weeks of SAM treatment produced a significant reduction in the rat striatal A2AR messenger RNA (mRNA) and protein content as well as A2AR-mediated signaling. Furthermore, when the content of 5-methylcytosine levels in the 5′UTR region of ADORA2A was analyzed, this was significantly increased in the striatum of SAM-treated animals; thus, an unambiguous correlation between SAM-mediated methylation and striatal A2AR expression could be established. Overall, we concluded that striatal A2AR functionality can be controlled by SAM treatment, an issue that might be relevant for the management of these neurological conditions that course with increased A2AR expression. |
| Keywords: | S-adenosyl-L-Methionine SAM ADORA2A Adenosine A2A receptor Methylcytosine Striatum |
| 本文献已被 SpringerLink 等数据库收录！ | |