title: Regulation of ecto-5'-nucleotidase (CD73) in cultured cortical astrocytes by different inflammatory factors.
abstract: 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-α (TNF-α), interferon-γ (IFN-γ), glutamate (Glu) and hydrogen peroxide (H(2)O(2)) 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-γ, LPS, Glu and H(2)O(2) decrease, while TNF-α 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.
authors: Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Serbia.
authors: Dusica
authors: D
authors: Brisevac
authors: Ivana
authors: I
authors: Bjelobaba
authors: Aleksandar
authors: A
authors: Bajic
authors: Tim
authors: T
authors: Clarner
authors: Mirjana
authors: M
authors: Stojiljkovic
authors: Cordian
authors: C
authors: Beyer
authors: Pavle
authors: P
authors: Andjus
authors: Markus
authors: M
authors: Kipp
authors: Nadezda
authors: N
authors: Nedeljkovic
mesh_terms: D015720:5'-Nucleotidase / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018836:Inflammation Mediators; D015720:5'-Nucleotidase