title: Modulation of the platelet-derived-growth-factor-induced calcium signal by extracellular/intracellular pH in Syrian hamster embryo cells. Implications for the role of calcium in mitogenic signalling.
abstract: Studies have been performed to understand the interactions and the role which intracellular calcium and intracellular pH have in mediating mitogen-stimulated cellular proliferation. Stimulation of Syrian hamster embryo (SHE) cells with the mitogen platelet-derived growth factor A/B (PDGF) results in intracellular acidification and capacitative calcium entry involving the intracellular release of calcium via the inositol trisphosphate gamma receptor calcium channel, followed by an extracellular influx of calcium through a dihydropyridine-sensitive plasma membrane calcium channel. Chronic extracellular/intracellular acidification results in the inactivation of both these calcium channels due to slowly reversible protein alterations. Paradoxically, transient intracellular acidification, like that following PDGF stimulation, could not stimulate the activation of either calcium channel. In addition, even though intracellular calcium fluxes by themselves could intiate intracellular acidification, loss of the PDGF-induced calcium signal did not result in the loss of the PDGF-induced transient intracellular acidification. Importantly with regard to the role intracellular calcium and pH have in mediating the mitogenic signal leading to cellular proliferation, chronic extracellular/intracellular acidification, which leads to a complete loss of the PDGF-induced calcium signal, did not result in the loss of PDGF-induced mitogenesis. These results indicate that the PDGF-induced calcium signal is not essential for PDGF-stimulated mitogenesis in Syrian hamster embryo cells. In contrast, blocking the PDGF-induced transient intracellular acidification completely blocks PDGF-induced mitogenesis, indicating that the mitogen-induced transient intracellular acidification, unlike the intracellular calcium ion signal, is indispensible for cellular proliferation in Syrian hamster embryo cells.
authors.affiliation: CP&RSD/HSD, Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45239-8707, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Isfort
authors.forename: S B
authors.initials: SB
authors.lastname: Stuard
authors.forename: D B
authors.initials: DB
authors.lastname: Cody
authors.forename: G M
authors.initials: GM
authors.lastname: Ridder
authors.forename: R A
authors.initials: RA
authors.lastname: LeBoeuf
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D005110:Extracellular Space / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007424:Intracellular Fluid / Q000378:metabolism; D008647:Mesocricetus; D008934:Mitogens / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D020960:omega-Conotoxins
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008934:Mitogens; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D018160:Receptors, Cytoplasmic and Nuclear; D020960:omega-Conotoxins; C087968:omega-conotoxin TVIA; D002110:Caffeine; D014443:Tyrosine; D015544:Inositol 1,4,5-Trisphosphate; D014700:Verapamil; D017479:Receptors, Platelet-Derived Growth Factor; D002118:Calcium