title: Transcriptional suppression of human apolipoproteinA4 and apolipoproteinC3 genes by phorbol myristate acetate in hepatic and intestinal cells.
abstract: BACKGROUND
  Genetic, epidemiological and clinical evidence has demonstrated the importance of the human apolipoproteinA5 (apoA5), apolipoproteinA4 (apoA4), apolipoproteinC3 (apoC3), and apolipoproteinA1 (apoA1) genes in the control of the triglyceride and cholesterol concentrations in the blood. However, little is known about the mechanism by which protein kinase C (PKC) regulates the expression of these genes in hepatic and intestinal cells. The aim of this study was to explore the regulatory role of PKC on the expression of apoA5, apoA4, apoC3 and apoA1.
  
  
  METHODS
  Hepatic HepG2 and intestinal Caco-2 cells were treated with a potent PKC activator, Phorbol myristate acetate (PMA). The real time quantitative RT-PCR (qRT-PCR) technique was used to evaluate the effects of PMA on the expression of apoA1, apoA4, apoA5 and apoC3 genes. Nuclear run on assay was used to determine whether the effect of PMA on apoA4 and apoC3 was due to its ability to regulate the transcription of these genes.
  
  
  RESULTS
  PMA specifically down-regulated the transcription of apoA4 and apoC3, but exhibited no effects on apoA1 or apoA5 in either HepG2 or Caco-2 cells. Further study by nuclear run on assay proved that the suppressive effect of PMA on apoA4 and apoC3 resulted from PMA's regulation of the transcription rate of the two genes.
  
  
  CONCLUSIONS
  PMA down-regulated transcription of apoA4 and apoC3 possibly through the common regulatory element shared by these two genes, suggesting a suppressive role of PKC on the transcriptional regulation of specific apolipoproteins in hepatic and intestinal cells.
authors.affiliation: Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin, University, Changchun, China First Hospital of Jilin Chemical Group Corporation, General Hospital, Jilin, China.
authors.forename: Guangping
authors.initials: G
authors.lastname: Li
authors.forename: Hongfa
authors.initials: H
authors.lastname: Yang
authors.forename: Wenxue
authors.initials: W
authors.lastname: Li
authors.forename: Shanshan
authors.initials: S
authors.lastname: Qu
authors.forename: Xue-Yao
authors.initials: XY
authors.lastname: Wang
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Ronggui
authors.initials: R
authors.lastname: Li
authors.forename: Zonggui
authors.initials: Z
authors.lastname: Wang
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000378:metabolism*; D001054:Apolipoproteins A / Q000378:metabolism*; D018938:Caco-2 Cells; D002467:Cell Nucleus / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D005810:Multigene Family; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D012333:RNA, Messenger; C022205:apolipoprotein A-IV; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate
keywords: Phorbol myristate acetate; apolipoproteins; multigene cluster; transcription