title: Regulation of neuropathy target esterase by the cAMP/protein kinase A signal.
abstract: 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.
authors.affiliation: Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, PR China.
authors.forename: Jia-Xiang
authors.initials: JX
authors.lastname: Chen
authors.forename: Ding-Xin
authors.initials: DX
authors.lastname: Long
authors.forename: Wei-Yuan
authors.initials: WY
authors.lastname: Hou
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans
chemical_list: D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase