title: Serum amyloid A induces WISH cell apoptosis.
abstract: OBJECTIVE
  Serum amyloid A (SAA) is an important mammalian acute reactant. Here, we aim to investigate the effect of SAA on apoptosis and its mechanism of action in human amniotic WISH cells.
  
  
  METHODS
  The expression of formyl peptide receptor (FPRL1), which is reported as a SAA receptor, was tested using RT-PCR and ligand binding assay with radio-labeled FPRL1 ligand. The effect of SAA on proliferating cell population was evaluated by thymidine incorporation assay. The protein phosphorylation levels and caspase-3 activity were detected by Western blot assay.
  
  
  RESULTS
  SAA inhibits thymidine incorporation in human amniotic WISH cells. A SAA-induced decrease of proliferating cell population was accompanied with nuclear condensation and caspase-3 activation in WISH cells, suggesting that SAA induces WISH cell apoptosis. Since FPRL1 has been reported as a SAA receptor, we investigated the effects of several FRPL1 agonists on a proliferating cell population in WISH cells. Among the tested FPRL1 agonists, only SAA induced a decrease of proliferating cell population in WISH cells. On the downstream signaling of SAA, we found that SAA stimulated extracellular signal-regulated kinase and p38 kinase, which were not inhibited by pertussis toxin (PTX), ruling out the role of PTX-sensitive G-proteins. Furthermore a SAAinduced decrease of proliferating cell population was not affected by PTX, suggesting that SAA inhibits WISH cell apoptosis in a PTX-sensitive G-proteinindependent manner. A SAA-induced decrease of a proliferating cell population was completely blocked by PD98059 and SB203580, suggesting that mitogenactivated protein kinase activities are essentially required for the process.
  
  
  CONCLUSIONS
  SAA is a novel inducer for WISH cell apoptosis, and the PTX-insensitive pathway is involved in the process.
authors.affiliation: Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Busan 602714, Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Jo
authors.forename: Jeanho
authors.initials: J
authors.lastname: Yun
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Chuhee
authors.initials: C
authors.lastname: Lee
authors.forename: Suk-Hwan
authors.initials: SH
authors.lastname: Baek
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000650:Amnion / Q000166:cytology / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011869:Radioligand Assay; D044042:Receptors, Formyl Peptide / Q000235:genetics* / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C105101:FPR2 protein, human; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D000685:Serum Amyloid A Protein; D037342:Pertussis Toxin; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one