Regulation of neuropathy target esterase by the cAMP/protein kinase A signal

As a phospholipase B, neuropathy target esterase (NTE) is responsible for the conversion of phosphatidylcholine (PC) to glycerophosphocholine (GPC). We examined the role of cAMP in the regulation of NTE in mammalian cells. Endogenous NTE activity was increased by cAMP-elevating chemicals, including...

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Bibliographic Details
Published in:Pharmacological research 2010-09, Vol.62 (3), p.259-264
Main Authors: Chen, Jia-Xiang, Long, Ding-Xin, Hou, Wei-Yuan, Li, Wei, Wu, Yi-Jun
Format: Article
Language:English
Subjects:
Adenyl cyclase
cAMP
Carboxylic Ester Hydrolases - genetics
Carboxylic Ester Hydrolases - metabolism
Cyclic AMP - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
Gene Expression Regulation
Glycerophosphocholine
HeLa Cells
Humans
Mammalian cell
Neuropathy target esterase
Protein kinase A
Regulatory mechanism
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Summary:As a phospholipase B, neuropathy target esterase (NTE) is responsible for the conversion of phosphatidylcholine (PC) to glycerophosphocholine (GPC). We examined the role of cAMP in the regulation of NTE in mammalian cells. Endogenous NTE activity was increased by cAMP-elevating chemicals, including dibutyryl cAMP, forskolin and forskolin plus 1-isobutyl-3-methylxanthine (IBMX), but decreased by the adenyl cyclase inhibitor SQ22536 which can reduce intracellular cAMP levels. Exogenous GFP-tagged NTE activity was not affected by changes in intracellular cAMP. NTE protein levels were up-regulated by the cAMP-elevating reagents and down-regulated by the inhibitor. The effect of the adenyl cyclase activator forskolin on NTE protein and mRNA levels was blocked by pretreatment with the protein kinase A (PKA) activity inhibitor H89. In addition, we found that changes in GPC, but not PC, levels were correlated with cAMP induced changes in NTE activity. These results are the first evidence that cAMP/PKA signals regulate NTE expression and GPC content in mammalian cells.
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2010.03.006