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Nitric oxide (NO) plays an important role as a signaling molecule in the proliferation of placenta trophoblasts. In this study, we investigated the effect of NO on the activation of phospholipase C (PLC) in BeWo cells, choriocarcinoma cell line. Sodium nitroprusside (SNP), an agent to produce NO spontaneously in cells, alone increased [3H]thymidine incorporation of BeWo cells, indicating NO stimulates proliferation of the cells. NO-induced proliferation of BeWo cells was blocked by U73122, an inhibitor of PLC, suggesting that NO-induced PLC activation is involved in the cell proliferation. NO also stimulated extracellular signal-regulated kinase (ERK) in BeWo cells, indicated by increased phosphorylation of ERK1/2 in Western blotting using anti-phospho-ERK1/2 antibody. NO-induced phosphorylation of ERK1/2 was not abrogated by U73122. PLCγ1 but not PLCγ2 was tyrosine phosphorylated by SNP in immunoprecipitation assay using anti-PLCγ1/PLCγ2 antibodies, and SNP-induced phosphorylation of PLCγ1 was abrogated by pre-treatment of cells with genistein and PD98059, indicating that NO induced-phosphorylation of PLCγ1 is mediated by ERK. These results suggest that NO stimulates the proliferation of BeWo cells through ERK and PLCγ1.
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UCI(KEPA) : I410-ECN-0101-2009-470-014220969