title: Serotonin inhibits apoptosis of pulmonary artery smooth muscle cell by pERK1/2 and PDK through 5-HT1B receptors and 5-HT transporters.
abstract: BACKGROUND
  Decreased apoptosis of pulmonary artery smooth muscle cells (PASMCs) plays a key role in pulmonary vascular remodeling in pulmonary hypertension (PH). However, the cause and mechanism of this decrease in apoptosis are still unclear. Serotonin (5-HT) has been shown to be involved in PH by inducing PASMC proliferation through the activation of 5-HT1B receptors (5-HT1BR) and 5-HT transporter (5-HTT). 5-HT1BR and 5-HTT are also involved in abnormal apoptosis in many other pathological processes. Therefore, we hypothesized that 5-HT induces decreases in PASMC apoptosis through 5-HT1BR and 5-HTT.
  
  
  METHODS
  PASMCs were treated with 5-HT, and their proliferation and apoptosis were assayed. 5-HT1BR agonists, 5-HT1BR antagonist, 5-HTT antagonist, combined 5-HT1BR/5-HTT antagonists, extracellular signal-regulated kinase (ERK1/2) activation inhibitor peptide I (EPI) and pyruvate dehydrogenase kinase (PDK) inhibitor sodium dichloroacetate (DCA) were used to explore the mechanism by which 5-HT induce decrease in PASMC apoptosis.
  
  
  RESULTS
  PASMCs stimulated by 5-HT showed an increase in proliferation and a decrease in apoptosis, accompanied by increase in pERK1/2, PDK, and mitochondrial transmembrane potential. The effects of 5-HT on the proliferation and apoptosis of PASMCs were similar to those of 5-HT1BR agonists and were markedly prevented by 5-HT1BR antagonist, 5-HTT antagonist, combined 5-HT1BR/5-HTT antagonists, EPI, or DCA.
  
  
  CONCLUSIONS
  5-HT inhibits PASMC apoptosis through 5-HT1BR or 5-HTT. pERK1/2 and PDK are involved in the process of 5-HT inhibition PASMC apoptosis through 5-HT1BR or 5-HTT.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.forename: Hong Yan
authors.initials: HY
authors.lastname: Tian
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Yan
authors.forename: Fen Ling
authors.initials: FL
authors.lastname: Fan
authors.forename: Wen Ping
authors.initials: WP
authors.lastname: Wang
authors.forename: Jun Li
authors.initials: JL
authors.lastname: Han
authors.forename: Jun-Bo
authors.initials: JB
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C470302:HTR1B protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D044302:Receptor, Serotonin, 5-HT1B; C493230:SLC6A4 protein, human; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D017346:Protein Serine-Threonine Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Apoptosis; Pulmonary artery smooth muscle cell; Serotonin