Extracellular ATP Selectively Upregulates Ecto-Nucleoside Triphosphate Diphosphohydrolase 2 and Ecto-5'-Nucleotidase by Rat Cortical Astrocytes In Vitro
2015
Аутори:
Brisevac, DusicaAdzic, Marija
Laketa, Danijela
Parabucki, Ana
Milosevic, Milena
Lavrnja, Irena
Bjelobaba, Ivana
Sevigny, Jean
Kipp, Markus
Nedeljkovic, Nadezda
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Extracellular ATP (eATP) 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 eATP 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 (eATP). At the transcriptional level, eATP 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, eATP altered membrane topology of eN, from clusters
localized in membrane domains to continuous distribution along the cell
membrane. Our results suggest that eATP, 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.
Кључне речи:
Reactive astrogliosis; Extracellular ATP; Ecto-nucleotidase; Ecto-5 `-nucleotidase/CD73Извор:
Journal of Molecular Neuroscience, 2015, 57, 3, 452-462
DOI: 10.1007/s12031-015-0601-y
ISSN: 1559-1166