Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 61, Issue 5, Pages 681-688Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2012.06.017
Keywords
Ecto-5 '-nucleotidase (CD73); Astrocytes; ATP; Adenosine; Inflammation
Categories
Funding
- Serbian Ministry for Education and Science Project [III41014]
- Bilateral Project between DAAD/Serbian Ministry of Science and Education
- DAAD
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Ecto-5'-nucleotidase (e-5NT) is a cell-surface located, rate-limiting enzyme in the extracellular metabolism of ATP, catalyzing the final step of the conversion of AMP to adenosine. Since this enzyme shifts the balance from pro-inflammatory ATP to anti-inflammatory adenosine, it is considered to be an important regulator of inflammation. Although up-regulation of e-5NT was repeatedly reported in several in vivo models of brain injury, the regulation of its expression and function remains largely unknown. We have studied effects of several pro-inflammatory factors, namely, bacterial endotoxin lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), glutamate (Glu) and hydrogen peroxide (H2O2) on e-5NT (i) activity, (ii) mRNA expression and (iii) membrane protein abundance in primary cultured cortical astrocytes. We are clearly able to demonstrate a stimulus-specific regulation of the e-5NT pathway. IFN-gamma, LPS, Glu and H2O2 decrease, while TNF-alpha increases e-5NT activity. The analysis of e-5NT gene expression and e-5NT membrane protein levels revealed that tested factors regulate e-5NT at different levels and by employing different mechanisms. In summary, we provide evidence that e-5NT activity is tightly regulated in a stimulus-specific manner. (C) 2012 Elsevier Ltd. All rights reserved.
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