Platelet-derived growth factor stimulates phospholipase C-gamma 1, extracellular signal-regulated kinase, and arachidonic acid release in rat myometrial cells: contribution to cyclic 3',5'-adenosine monophosphate production and effect on cell proliferation

Autor: S. Harbon, Denis Leiber, Isaline Boulven, Monique Vacher, Bruno Palmier, Philippe Robin
Rok vydání: 2001
Předmět:
Indomethacin
Becaplermin
Prostacyclin
chemistry.chemical_compound
1-Methyl-3-isobutylxanthine
Cyclic AMP
GTP-Binding Protein alpha Subunits
Gs
Cells
Cultured
Mitogen-Activated Protein Kinase 1
Platelet-Derived Growth Factor
Forskolin
Arachidonic Acid
Mitogen-Activated Protein Kinase 3
biology
Drug Synergism
General Medicine
Proto-Oncogene Proteins c-sis
Cell biology
Isoenzymes
Myometrium
Arachidonic acid
Female
Mitogen-Activated Protein Kinases
Platelet-derived growth factor receptor
Cell Division
medicine.drug
medicine.medical_specialty
Inositol Phosphates
Prostaglandin
Arachidonic Acids
Phospholipases A
Internal medicine
medicine
Animals
Cyclooxygenase Inhibitors
Rats
Wistar
Phosphotyrosine
Phospholipase C
Colforsin
Inositol trisphosphate
Tyrosine phosphorylation
Cell Biology
Epoprostenol
Rats
Enzyme Activation
Endocrinology
Reproductive Medicine
chemistry
Type C Phospholipases
biology.protein
Zdroj: Biology of reproduction. 65(2)
ISSN: 0006-3363
Popis: In the present study, we examined downstream signaling events that followed exposure of cultured rat myometrial cells to platelet-derived growth factor (PDGF) and their effect on cell proliferation. PDGF-BB induced tyrosine phosphorylation of PDGF-beta receptors and increased inositol trisphosphate production via the tyrosine phosphorylation of phospholipase (PL)C-gamma 1. PDGF-BB also increased cAMP synthesis. This increase was potentiated by forskolin and reduced by indomethacin, a cyclooxygenase inhibitor, reflecting a Gs protein-mediated process via prostaglandin biosynthesis. The prostaglandin produced by PDGF was characterized as prostacyclin (PGI(2)). PDGF-BB increased arachidonic acid (AA) release, which, similarly to cAMP accumulation, was abolished in the presence of AACOCF3, a cytosolic PLA(2) inhibitor, and in the absence of Ca(2+). U-73122, a potent inhibitor of PLC activity, blocked both the production of inositol phosphates and the AA release triggered by PDGF-BB. Extracellular signal-regulated kinases (ERKs) 1 and 2 are expressed in myometrial cells, and PDGF-BB selectively activated ERK2. PD98059, an inhibitor of the ERK-activating kinase, blocked PDGF-BB-mediated ERK2 activation, AA release, and cAMP production. The results demonstrate that PDGF-BB stimulated cAMP formation through both PLC activation and ERK-dependent AA release and PGI(2) biosynthesis. PDGF-BB also increased cell proliferation and [(3)H]thymidine incorporation. This was abolished by PD98059, demonstrating that the ERK cascade is required for the mitogenic effect of PDGF-BB. Forskolin, which potentiated the cAMP response to PDGF-BB, attenuated both DNA synthesis and ERK activation triggered by PDGF-BB, suggesting the presence of a negative feedback regulation.
Databáze: OpenAIRE
Externí odkaz: