Extracellular ATP Selectively Upregulates Ecto-Nucleoside Triphosphate Diphosphohydrolase 2 and Ecto-5′-Nucleotidase by Rat Cortical Astrocytes In Vitro

• Published in: Journal of molecular neuroscience Vol. 57; no. 3; pp. 452 - 462
• Main Authors: Brisevac, Dusica, Adzic, Marija, Laketa, Danijela, Parabucki, Ana, Milosevic, Milena, Lavrnja, Irena, Bjelobaba, Ivana, Sévigny, Jean, Kipp, Markus, Nedeljkovic, Nadezda
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2015; Springer Nature B.V
• Subjects: 5'-Nucleotidase - biosynthesis; 5'-Nucleotidase - genetics; Adenosine - metabolism; Adenosine triphosphate; Adenosine Triphosphate - metabolism; Adenosine Triphosphate - pharmacology; Animals; Antigens; Astrocytes - drug effects; Astrocytes - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Division; Cell Membrane - drug effects; Cell Membrane - enzymology; Cells, Cultured; Cerebral Cortex - cytology; Cytokines; Enzyme Induction - drug effects; Enzymes; Gliosis - enzymology; Morphology; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neurochemistry; Neurology; Neurosciences; Phosphoric Diester Hydrolases - biosynthesis; Phosphoric Diester Hydrolases - genetics; Primary Cell Culture; Protein Biosynthesis - drug effects; Proteins; Proteomics; Pyrophosphatases - biosynthesis; Pyrophosphatases - genetics; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Signal transduction; Signal Transduction - drug effects; Signal Transduction - physiology; Transcription, Genetic - drug effects; Tumor necrosis factor-TNF; Up-Regulation - drug effects; Serbia; Canada; Reactive astrogliosis; NTPDase2/CD39L1; Ecto-nucleotidase; Ecto-5′-nucleotidase/CD73; Extracellular ATP
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-015-0601-y

Extracellular ATP ( e ATP) acts as a danger-associated molecular pattern which induces reactive response of astrocytes after brain insult, including morphological remodeling of astrocytes, proliferation, chemotaxis, and release of proinflammatory cytokines. The responses induced by e ATP are under control of ecto-nucleotidases, which catalyze sequential hydrolysis of ATP to adenosine. In the mammalian brain, ecto-nucleotidases comprise three enzyme families: ecto-nucleoside triphosphate diphosphohydrolases 1–3 (NTPDase1–3), ecto-nucleotide pyrophosphatase/phospodiesterases 1–3 (NPP1–3), and ecto-5′-nucleotidase (eN), which crucially determine ATP/adenosine ratio in the pericellular milieu. Altered expression of ecto-nucleotidases has been demonstrated in several experimental models of human brain dysfunctions. In the present study, we have explored the pattern of NTPDase1–3, NPP1–3, and eN expression by cultured cortical astrocytes challenged with 1 mmol/L ATP ( e ATP). At the transcriptional level, e ATP upregulated expression of NTPDase1, NTPDase2, NPP2, and eN, while, at translational and functional levels, these were paralleled only by the induction of NTPDase2 and eN. Additionally, e ATP altered membrane topology of eN, from clusters localized in membrane domains to continuous distribution along the cell membrane. Our results suggest that e ATP, by upregulating NTPDase2 and eN and altering the enzyme membrane topology, affects local kinetics of ATP metabolism and signal transduction that may have important roles in the process related to inflammation and reactive gliosis.