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Expression of Ecto-Nucleoside Triphosphate Diphosphohydrolase1-3 (NTPDase1–3) by Cortical Astrocytes After Exposure to Pro-inflammatory Factors In Vitro

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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.

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Acknowledgments

The authors are grateful to Dr. Terence L. Kirley for generous gift of KLH14 antisera used in the study. This work was supported by Serbian Ministry for Education and Science Project No. III41014 and Bilateral Project between DAAD/Serbian Ministry of Education and Science. D.B. was supported by DAAD financed Scientific Internship in Germany for Undergraduates and Graduates from Serbia. T.C. was supported by a START grant of RWTH Aachen University, Medical Faculty.

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Authors and Affiliations

  1. Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski trg 3, 11001, Belgrade, Serbia

    Dusica Brisevac, Aleksandar Bajic, Milena Milosevic & Nadezda Nedeljkovic

  2. Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Belgrade, Serbia

    Ivana Bjelobaba & Mirjana Stojiljkovic

  3. Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Aachen, Germany

    Cordian Beyer, Tim Clarner & Markus Kipp

Authors
  1. Dusica Brisevac
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  2. Aleksandar Bajic
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  3. Ivana Bjelobaba
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  4. Milena Milosevic
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  5. Mirjana Stojiljkovic
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  6. Cordian Beyer
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  7. Tim Clarner
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  8. Markus Kipp
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  9. Nadezda Nedeljkovic
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Correspondence to Nadezda Nedeljkovic.

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Brisevac, D., Bajic, A., Bjelobaba, I. et al. Expression of Ecto-Nucleoside Triphosphate Diphosphohydrolase1-3 (NTPDase1–3) by Cortical Astrocytes After Exposure to Pro-inflammatory Factors In Vitro. J Mol Neurosci 51, 871–879 (2013). https://doi.org/10.1007/s12031-013-0088-3

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  • DOI: https://doi.org/10.1007/s12031-013-0088-3

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