Document Detail

Reduced viability of neuronal cells after overexpression of protein histidine phosphatase.
MedLine Citation:
PMID:  18656514     Owner:  NLM     Status:  MEDLINE    
Protein histidine phosphatase (PHP) has just recently been discovered in eukaryotes and ATP-citrate lyase (ACL) was shown to be one of its substrates. Since ACL is crucial for cellular energy and fat metabolism we made an attempt to study the influence of PHP on cell viability. Using an adenoviral vector PHP was overexpressed in SN56 cholinergic murine neuroblastoma cells and in primary cultures of hippocampal neurons obtained from embryonic rats (E18). Overexpression of PHP in these cells caused a decrease in ACL activity and consequently impaired viability. To be sure that the reduced cellular viability was achieved by overexpression of PHP we also downregulated ACL in SN56 cells using RNAi-technology. Downregulation of ACL was harmful to the cells similar to what was observed upon overexpression of PHP. Taken together, it is concluded that overexpression of PHP results in increased dephosphorylation with concomitant inactivation of ACL, thus finally leading to cell damage.
Josef Krieglstein; Martina Lehmann; Anette Mäurer; Thomas Gudermann; Olaf Pinkenburg; Thomas Wieland; Sarah Litterscheid; Susanne Klumpp
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-04
Journal Detail:
Title:  Neurochemistry international     Volume:  53     ISSN:  0197-0186     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-16     Completed Date:  2009-02-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  132-6     Citation Subset:  IM    
Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universitaet, Hittorfstrasse 58-62, D-48149 Münster, Germany.
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MeSH Terms
ATP Citrate (pro-S)-Lyase / genetics,  metabolism
Adenoviridae / genetics
Cell Line
Cell Line, Tumor
Cell Survival
Embryo, Mammalian / cytology
Neurons / cytology*,  enzymology
Phosphoric Monoester Hydrolases / biosynthesis*,  genetics
RNA, Small Interfering / genetics
Rats, Sprague-Dawley
Reg. No./Substance:
0/RNA, Small Interfering; EC Citrate (pro-S)-Lyase; EC 3.1.3.-/PHPT1 protein, human; EC 3.1.3.-/Phosphoric Monoester Hydrolases

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