Regulation of ecto-5¡ä-nucleotidase (CD73) in cultured cortical astrocytes by different inflammatory factors

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• 作者：Dusica Brisevac ; Ivana Bjelobaba ; Aleks ; ar Bajic ; Tim Clarner ; Mirjana Stojiljkovic ; Cordian Beyer ; Pavle Andjus ; Markus Kipp ; Nadezda Nedeljkovic
• 关键词：Ecto-5&prime ; -nucleotidase (CD73) ; Astrocytes ; ATP ; Adenosine ; Inflammation
• 刊名：Neurochemistry International
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：61
• 期：5
• 页码：681-688
• 全文大小：738 K

文摘

Ecto-5¡ä-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-¦Á (TNF-¦Á), interferon-¦Ã (IFN-¦Ã), 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-¦Ã, LPS, Glu and H₂O₂ decrease, while TNF-¦Á 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.