title: CXCL12 Regulates the Cholinergic Locus and CHT1 Through Akt Signaling Pathway.
abstract: BACKGROUND
  CXCL12 is pivotal for cholinergic neurons, and it induces the expressions of several genes that are essential for synthesis and storage of acetylcholine(ACh), specifically choline acetyltransferase, vesicular ACh transporter (VAChT), and choline transporter. The present study explored the impact of pharmacological Akt inhibition upon cholinergic gene expression.
  
  
  METHODS
  Western blotting was employed to determine the level of p-AKT, RT-PCR to check the mRNA levels of and CHT1(choline transporter1),VAChT and ChAT, ELISA to decipher the secretion of ACh and the activity of choline acetyltransferase.
  
  
  RESULTS
  Here we demonstrated, in the rat pheochromocytoma cell line PC12 and in primary rat neuronal cultures, that CXCL12-evoked up-regulation of CHT1, VAChT and ChAT was mediated by Akt. Inhibition of Akt by the pharmacological inhibitor GSK690693 eliminated CXCL12-stimulated increases in cholinergic gene expression. Moreover, treatment with GSK690693 reversed CXCL12-evoked increases in choline acetyltransferase activity and ACh production.
  
  
  CONCLUSIONS
  Our results suggest that CXCL12 contributes to cholinergic gene expression via Akt signaling pathway.
authors.affiliation: Xinxiang medical university, Xinxiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhao
authors.forename: Meixia
authors.initials: M
authors.lastname: Guo
authors.forename: Xuefei
authors.initials: X
authors.lastname: Han
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Feng
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001596:Benzylamines; D027682:Cation Transport Proteins / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D000080027:Cyclams; D005786:Gene Expression Regulation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006017:Glycolipids / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C577331:1-(6-hydroxymethylinositol)-2-O-methyl-3-O-octadecyl-sn-glycerocarbonate; D001596:Benzylamines; C501512:CHT1 protein, rat; D027682:Cation Transport Proteins; D054377:Chemokine CXCL12; D000080027:Cyclams; C528328:GSK690693; D006017:Glycolipids; D006571:Heterocyclic Compounds; D010069:Oxadiazoles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D002795:Choline O-Acetyltransferase; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D002794:Choline; D000109:Acetylcholine; C088327:plerixafor