Serum amyloid A induces WISH cell apoptosis.

Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 100956087 Publication Model: Print Cited Medium: Print ISSN: 1671-4083 (Print) Linking ISSN: 16714083 NLM ISO Abbreviation: Acta Pharmacol Sin Subsets: MEDLINE

Publication: 2009- : New York : Nature Publishing Group
Original Publication: Beijing, China : Science Press, c2000-

Apoptosis/*drug effects ; Receptors, Formyl Peptide/*genetics ; Receptors, Lipoxin/*genetics ; Serum Amyloid A Protein/*pharmacology; Amnion/cytology ; Amnion/metabolism ; Blotting, Western ; Caspase 3/metabolism ; Cell Line ; Cell Proliferation/drug effects ; Flavonoids/pharmacology ; Gene Expression/drug effects ; Humans ; Imidazoles/pharmacology ; Mitogen-Activated Protein Kinases/metabolism ; Pertussis Toxin/pharmacology ; Phosphorylation/drug effects ; Pyridines/pharmacology ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Radioligand Assay ; Receptors, Formyl Peptide/metabolism ; Receptors, Lipoxin/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; p38 Mitogen-Activated Protein Kinases/metabolism

Aim: 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.
Conclusion: SAA is a novel inducer for WISH cell apoptosis, and the PTX-insensitive pathway is involved in the process.

0 (FPR2 protein, human)
0 (Flavonoids)
0 (Imidazoles)
0 (Pyridines)
0 (RNA, Messenger)
0 (Receptors, Formyl Peptide)
0 (Receptors, Lipoxin)
0 (Serum Amyloid A Protein)
EC 2.4.2.31 (Pertussis Toxin)
EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
EC 3.4.22.- (Caspase 3)
OU13V1EYWQ (SB 203580)
SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)

Date Created: 20061223 Date Completed: 20080317 Latest Revision: 20180815

20240829

10.1111/j.1745-7254.2007.00475.x

17184585