期刊
JOURNAL OF MOLECULAR NEUROSCIENCE
卷 51, 期 3, 页码 871-879出版社
HUMANA PRESS INC
DOI: 10.1007/s12031-013-0088-3
关键词
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资金
- Serbian Ministry for Education and Science [III41014]
- DAAD/Serbian Ministry of Education and Science
- DAAD in Germany
- DAAD in Serbia
- START grant of RWTH Aachen University, Medical Faculty
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-gamma, TNF-alpha, LPS, peroxide, and glutamate) on NTPDase1-3 activity and expression by cultured cortical astrocytes. We were able to demonstrate that INF-gamma and TNF-alpha increased both ATP and ADP hydrolysis, while LPS specifically increased ATP hydrolysis. Consistent with the observed enhanced nucleotidase activity, INF-gamma induced the upregulation of NTPDase1 at the mRNA and protein level. Furthermore, we were able to demonstrate that INF-gamma and TNF-alpha decreased the relative abundance of dominant astrocytic NTPDase2 in favor of NTPDase1. In summary, these results suggest that INF-gamma, TNF-alpha, and LPS may be relevant in vivo regulators of NTPDase expression in neuropathologies associated with neuroinflammation.
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