title: Expression of ecto-nucleoside triphosphate diphosphohydrolase1-3 (NTPDase1-3) by cortical astrocytes after exposure to pro-inflammatory factors in vitro.
abstract: Nucleoside triphosphate diphosphohydrolases (NTPDases) are ecto-enzymes catalyzing the first step of sequential hydrolysis of extracellular ATP to adenosine, as the final product. Among eight members of NTPDase family, NTPDases1-3 have been shown to be expressed in the brain. Although altered NTPDase expression has been observed in relation to cell death and reactive gliosis in several experimentally induced neuropathologies, regulators of NTPDases expression and function are largely unknown. The present study explored the effects of several inflammatory factors (i.e., INF-γ, TNF-α, LPS, peroxide, and glutamate) on NTPDase1-3 activity and expression by cultured cortical astrocytes. We were able to demonstrate that INF-γ and TNF-α increased both ATP and ADP hydrolysis, while LPS specifically increased ATP hydrolysis. Consistent with the observed enhanced nucleotidase activity, INF-γ induced the upregulation of NTPDase1 at the mRNA and protein level. Furthermore, we were able to demonstrate that INF-γ and TNF-α decreased the relative abundance of dominant astrocytic NTPDase2 in favor of NTPDase1. In summary, these results suggest that INF-γ, TNF-α, and LPS may be relevant in vivo regulators of NTPDase expression in neuropathologies associated with neuroinflammation.
authors.affiliation: Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski trg 3, 11001, Belgrade, Serbia.
authors.forename: Dusica
authors.initials: D
authors.lastname: Brisevac
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Bajic
authors.forename: Ivana
authors.initials: I
authors.lastname: Bjelobaba
authors.forename: Milena
authors.initials: M
authors.lastname: Milosevic
authors.forename: Mirjana
authors.initials: M
authors.lastname: Stojiljkovic
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
authors.forename: Tim
authors.initials: T
authors.lastname: Clarner
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
authors.forename: Nadezda
authors.initials: N
authors.lastname: Nedeljkovic
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001081:Apyrase / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology*; D006868:Hydrolysis; D007371:Interferon-gamma / Q000494:pharmacology; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D011755:Pyrophosphatases; C027201:ectoATPase; C439652:nucleoside-triphosphate diphosphohydrolase 3; D001081:Apyrase; C067869:CD39 antigen