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rdf:type |
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lifeskim:mentions |
umls-concept:C0001443,
umls-concept:C0001492,
umls-concept:C0007587,
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0445450,
umls-concept:C0814999,
umls-concept:C0851285,
umls-concept:C1181031,
umls-concept:C1314939,
umls-concept:C1367453
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pubmed:issue |
6
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pubmed:dateCreated |
2006-5-31
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pubmed:abstractText |
Adenosine is generated in the microenvironment of emerging thymocytes through normal mechanisms of lymphocyte selection. In a normal thymus, most of the adenosine is catabolized by adenosine deaminase; however, in an environment where up to 95% of the cells undergo programmed cell death, a sufficient amount of adenosine is accumulated to trigger cell surface adenosine receptors. Here we show that accumulated adenosine can induce apoptosis in immature mouse thymocytes, mostly via adenosine A(2A) receptors. The signaling pathway is coupled to adenylate cyclase activation, induction of the Nur77 transcription factor, Nur77-dependent genes, such as Fas ligand and TRAIL, and the pro-apoptotic BH3-only protein Bim. We analyzed several knockout and transgenic mouse lines and found that adenosine-induced killing of mouse thymocytes requires Bim, occurs independently of "death receptor" signaling and is inhibited by Bcl-2 and Nur77. Collectively our data demonstrate that adenosine-induced cell death involves signaling pathways originally found in negative selection of thymocytes and suggest a determining role of Bim and a regulatory role for Nur77.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/BH3 Interacting Domain Death...,
http://linkedlifedata.com/resource/pubmed/chemical/Bid protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Fasl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nr4a1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 4...,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Adenosine A2A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Steroid,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0014-2980
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1559-71
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16673448-Adenosine,
pubmed-meshheading:16673448-Adenylate Cyclase,
pubmed-meshheading:16673448-Animals,
pubmed-meshheading:16673448-Apoptosis,
pubmed-meshheading:16673448-BH3 Interacting Domain Death Agonist Protein,
pubmed-meshheading:16673448-Blotting, Western,
pubmed-meshheading:16673448-Cyclic AMP,
pubmed-meshheading:16673448-DNA-Binding Proteins,
pubmed-meshheading:16673448-Fas Ligand Protein,
pubmed-meshheading:16673448-Male,
pubmed-meshheading:16673448-Membrane Glycoproteins,
pubmed-meshheading:16673448-Mice,
pubmed-meshheading:16673448-Mice, Inbred C57BL,
pubmed-meshheading:16673448-Mice, Knockout,
pubmed-meshheading:16673448-Mice, Transgenic,
pubmed-meshheading:16673448-Nuclear Receptor Subfamily 4, Group A, Member 1,
pubmed-meshheading:16673448-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:16673448-RNA, Messenger,
pubmed-meshheading:16673448-Receptor, Adenosine A2A,
pubmed-meshheading:16673448-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:16673448-Receptors, Steroid,
pubmed-meshheading:16673448-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16673448-T-Lymphocytes,
pubmed-meshheading:16673448-Transcription Factors,
pubmed-meshheading:16673448-Tumor Necrosis Factors
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pubmed:year |
2006
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pubmed:articleTitle |
Adenosine A2A receptor-mediated cell death of mouse thymocytes involves adenylate cyclase and Bim and is negatively regulated by Nur77.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Signaling and Apoptosis Research Group, Hungarian Academy of Sciences, Research Center of Molecular Medicine, University of Debrecen.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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