TY  - JOUR
AB  - 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.
AU  - Eißing, Anna
AU  - Fischer, Daniel
AU  - Rauch, Ilka
AU  - Baumann, Anne
AU  - Schebb, Nils Helge
AU  - Karst, Uwe
AU  - Rose, Karsten
AU  - Klumpp, Susanne
AU  - Krieglstein, Josef
DA  - 2012-03-21
DO  - doi:10.1186/1471-2202-13-31
LA  - eng
N1  - Finanziert durch den Open-Access-Publikationsfonds 2012/2013 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
N1  - BMC Neuroscience 13 (2012) 31
PY  - 2012-03-21
TI  - Acetylcholine content and viability of cholinergic neurons are influenced by the activity of protein histidine phosphatase
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-17379412093
Y2  - 2024-11-22T00:22:50
ER  -