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Acetylcholine content and viability of cholinergic neurons are influenced by the activity of protein histidine phosphatase

Background: The first mammalian protein histidine phosphatase (PHP) was discovered in the late 90s of the last century. One of the known substrates of PHP is ATP-citrate lyase (ACL), which is responsible - amongst other functions - for providing acetyl-CoA for acetylcholine synthesis in neuronal tissues. It has been shown in previous studies that PHP downregulates the activity of ACL by dephosphorylation. According to this our present work focused on the influence of PHP activity on the acetylcholine level in cholinergic neurons. Results: The amount of PHP in SN56 cholinergic neuroblastoma cells was increased after overexpression of PHP by using pIRES2-AcGFP1-PHP as a vector. We demonstrated that PHP overexpression reduced the acetylcholine level and induced cell death. The acetylcholine content of SN56 cells was measured by fast liquid chromatographytandem mass spectrometry method. Overexpression of the inactive H53A-PHP mutant also induced cell damage, but in a significantly reduced manner. However, this overexpression of the inactive PHP mutant did not change the acetylcholine content of SN56 cells significantly. In contrast, PHP downregulation, performed by RNAitechnique, did not induce cell death, but significantly increased the acetylcholine content in SN56 cells. Conclusions: We could show for the first time that PHP downregulation increased the acetylcholine level in SN56 cells. This might be a potential therapeutic strategy for diseases involving cholinergic deficits like Alzheimer’s disease.

Titel: Acetylcholine content and viability of cholinergic neurons are influenced by the activity of protein histidine phosphatase
Verfasser: Eissing, Anna Katharina GND
Fischer, Daniel
Rauch, Ilka
Baumann, Anne
Schebb, Nils Helge GND
Karst, Uwe
Rose, Karsten
Klumpp, Susanne
Krieglstein, Josef GND
Organisation: FB 12: Chemie und Pharmazie
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 21.03.2012
Publikation in MIAMI: 27.02.2013
Datum der letzten Änderung: 16.04.2019
Quelle: BMC Neuroscience 13 (2012) 31
Fachgebiete: Chemie
Lizenz: CC BY 2.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2012/2013 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-17379412093
DOI: doi:10.1186/1471-2202-13-31