Role of protein histidine phosphatase for viability of neuronal cells.
We recently found protein histidine phosphatase (PHP) in eukaryotes and identified ATP-citrate lyase (ACL) and the beta-subunit of G-proteins as its substrates. The aim of the present study was to get information on the significance of PHP for cellular function and viability. PHP was overexpressed by a viral vector in SH-SY5Y cells, a human neuroblastoma cell line, and in primary cultures of cortical neurons from embryonic (E19) rats. Furthermore, PHP was downregulated by siRNA in SH-SY5Y cells. We could demonstrate that overexpression of PHP decreased the phosphorylation state of ACL. Accordingly, the activity of ACL seemed to be reduced and subsequently, the viability of the cells was diminished. On the other hand, downregulation of PHP did not clearly influence phosphorylation and activity of ACL as well as viability of the cells. The results suggest that an increased activity of PHP impairs cellular function whereas downregulation of PHP does not.
Klumpp
Susanne
S
Institut fuer Pharmazeutische und Medizinische Chemie, Westfaelische Wilhelms-Universitaet, Hittorfstr. 58-62, D-48149 Muenster, Germany. k.secretary@uni-muenster.de
Faber
Daniela
D
Fischer
Daniel
D
Litterscheid
Sarah
S
Krieglstein
Josef
J
D000256:Adenoviridae; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D006801:Humans; D009474:Neurons / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D034741:RNA, Small Interfering; C504019:PHPT1 protein, human; C504020:Phpt1 protein, rat; D010744:Phosphoric Monoester Hydrolases