Phospholipase C axis is the preferential pathway leading to PKC activation following PTH or PTHrP stimulation in human term placenta.
Parathyroid-related peptide (PTHrP) is abundant in human syncytiotrophoblast where it was suggested to play an important role in maternal-fetal calcium homeostasis. On the other hand, parathyroid hormone (PTH), another hypercalcemic factor, would be implicated in the maintenance of the mother's calcium balance. In many cells, these hormones are associated to G-coupled receptors and activate protein kinase (PKC). Thus, the first aim of this study was to determine the cellular pathway (phospholipase; PLC and phosphatidyl-inositol-3 kinase; PI3K) leading to the activation of PKC following a PTH or PTHrP stimulation in brush border (BBM) and basal plasma membranes (BPM) of human term placenta. Both peptides were shown to be potent modulators of the PKC activity in these membranes with optimal concentrations of 10(-8)M and 10(-9)M for hPTH and hPTHrP, respectively. Furthermore, the use of bisindolylmaleimide (BIM), a non-selective PKC inhibitor, serves to demonstrate the specificity of the PKC-dependent MARCKS-psd phosphorylation. While LY-294002, a PI3K inhibitor failed to counteract the hPTH- and hPTHrP-induced PKC stimulation in BBM and BPM, U-73122, a PLC inhibitor, totally abolished the PKC stimulation by hPTH and hPTHrP. Taken together, these data suggest that the activation of PKC by hPTH or hPTHrP, in BBM and BPM, is preferentially associated to the PLC pathway rather than the PI3K's.
Laramée
Mélanie
M
Laboratoire de Physiologie Materno-Foetale, Département des Sciences Biologiques, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, H3C 3P8, Québec, Canada.
Simoneau
Lucie
L
Lafond
Julie
J
D000328:Adult; D002135:Calcium-Binding Proteins; D002462:Cell Membrane / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D005959:Glucosidases; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008301:Maleimides / Q000494:pharmacology; D008565:Membrane Proteins; D008871:Microvilli / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000378:metabolism; D010920:Placenta / Q000187:drug effects*; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction; D013268:Stimulation, Chemical; D014327:Trophoblasts / Q000187:drug effects / Q000201:enzymology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D004963:Estrenes; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008301:Maleimides; D008565:Membrane Proteins; D009025:Morpholines; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011493:Protein Kinase C; D010738:Type C Phospholipases; D005959:Glucosidases; C070368:PRKCSH protein, human; C088060:bisindolylmaleimide