期刊
JOURNAL OF NEUROCHEMISTRY
卷 112, 期 5, 页码 1273-1285出版社
WILEY
DOI: 10.1111/j.1471-4159.2009.06538.x
关键词
5-azacytidine; adenosine A(2A) receptor; CpG island; DNA methylation; S-adenosyl-l-methionine
资金
- Ministerio de Ciencia e Innovacion, Instituto de Salud Carlos III [PI05/1631, CP08/00095]
- European Union [MRTN-CT-2006-035810]
- Consejeria de Educacion y Ciencia [PCI08-0125]
- Consejeria de Sanidad-FISCAM [PI-2007/50, G-2007-C/13]
- Junta de Comunidades de Castilla-La Mancha
- Ministerio de Ciencia e Innovacion [BFU2008-00138]
- University of Barcelona
P>Adenosine A(2A) receptors (A(2A)Rs) appear to play important roles in inflammation and in certain diseases of the nervous system. Pharmacological modulation of A(2A)Rs is particularly useful in Parkinson's disease and has been tested in schizophrenia. However, little is known about the regulation of A(2A)R gene (ADORA2A). A bioinformatic analysis revealed the presence of three CpG islands in the 5' UTR region of human ADORA2A. Next, HeLa, SH-SY5Y and U87-MG cells were treated for 48 h with 5 mu M 5-azacytidine (Aza). Increased A(2A)R levels were demonstrated in HeLa and SH-SY5Y cells when compared with non-treated cells. No modifications were seen in U87-MG cells. The increased A(2A)R mRNA and protein levels were accompanied by a loss of DNA methylation pattern in HeLa and SH-SY5Y cells, as measured with the SEQUENOM MassArray platform. The Aza treatment also reduced the affinity of a methyl-CpG-binding protein for ADORA2A by quantitative chromatin immunoprecipitation in HeLa cells. Interestingly, A(2A)R levels were reduced by S-adenosyl-l-methionine treatment in U87-MG and methyl-CpG-binding protein affinity was increased for ADORA2A by quantitative chromatin immunoprecipitation. Therefore, these results show for the first time that DNA methylation plays a role in ADORA2A transcription and, subsequently, in constitutive A(2A)R cell surface levels.
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