title: [Protein kinase A signaling pathway participates in high glucose-induced inhibition of G6PD activity and respiratory burst dysfunction in THP-1 cells].
abstract: OBJECTIVE
  To observe the changes in glucose 6-phosphate dehydrogenase (G6PD) activity, cAMP and respiratory burst function in THP-1 cells exposed to high glucose and identify the possible signaling pathways to mediate these changes.
  
  
  METHODS
  THP-1 cells were treated with high glucose, high glucose plus the PKA inhibitor (PKI), or normal glucose plus Forskolin. The changes in the G6PD activity and cAMP in the exposed cells were assayed using the spectrophotometric method, and the reactive oxygen species (ROS) content in the cell culture was determined using the fluorescent probe DCFH-DA. Western blotting was employed to examine the expression of phosphorylated p47(phox) in the cells.
  
  
  RESULTS
  Compared with the normal control cells, the cells exposed to high glucose and to normal glucose and Forskolin showed a significantly lowered G6PD activity, ROS content and expression of phosphorylated p47(phox), but with a increased cAMP content (P<0.01). High glucose exposure in the presence of PKI caused no significant changes in G6PD activity, ROS level, phosphorylated p47(phox) or cAMP compared to those in the normal control cells (P>0.01).
  
  
  CONCLUSIONS
  High glucose causes inhibition of G6PD activity in THP-1 cells via activation of PKA and thus leads to respiratory burst dysfunction, which is the probable mechanism underlying the lowered leucocyte function and susceptibility to infections in diabetic patients.
authors.affiliation: Department of Endocrinology, Southern Medical University, Guangzhou, China. 13924011881@126.com
authors.forename: Huiyan
authors.initials: H
authors.lastname: Zeng
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Xue
mesh_terms: D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005947:Glucose / Q000009:adverse effects*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D016897:Respiratory Burst / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000242:Cyclic AMP; D005954:Glucosephosphate Dehydrogenase; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose