Participation of phospholipase A2 in induction of tissue plasminogen activator (t-PA) production by human fibroblast, IMR-90 cells, stimulated by proteose peptone.
Proteose peptone (p.peptone) had an ability to induce tissue plasminogen activator(t-PA) production by human embryonic lung fibroblast, IMR-90 cells. The induction was dependent on extracellular Ca2+ concentration. The stimulation of p.peptone caused uptake of 45Ca2+ by the cells. The presences of both p.peptone and Ca2+ in medium were necessary for the continuous induction of t-PA production. Hydrocortisone and dexamethasone inhibited t-PA production induced by p.peptone. In addition, the inhibitors of phospholipase A2, quinacrine and 4-bromophenacylbromide, respectively inhibited t-PA production as well as glucocorticoids. Conversely, melittin, an activator of phospholipase A2, induced t-PA production in a dose-dependent manner. Exogenous phospholipase A2 strongly induced t-PA production and also arachidonic acid moderately did in a dose-dependent manner. P.peptone stimulated the release of radioactive arachidonic acid from 3H-arachidonic acid-labeled IMR-90 cells under the presence of Ca2+. These results suggest that the induction of t-PA production by p.peptone is closely related to the activity of phospholipase A2, that is, the release of arachidonic acid from phospholipids in cell membrane.
Suzuki
A
A
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan.
Mitsuda
S
S
Higashio
K
K
Kumasaka
T
T
D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002364:Caseins / Q000494:pharmacology*; D002460:Cell Line; D004790:Enzyme Induction / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008555:Melitten / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010461:Peptones / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology*; D054467:Phospholipases A2; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000276:immunology
D002364:Caseins; D005938:Glucocorticoids; D010446:Peptide Fragments; D010461:Peptones; C018135:proteose-peptone; D008555:Melitten; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D010959:Tissue Plasminogen Activator; D002118:Calcium