Modulation of tissue plasminogen activator biosynthesis by phosphatidylinositol liposomes in human fetal lung fibroblasts.
Phosphatidylinositol (PI) liposomes at 40 microM increased tissue plasminogen activator (t-PA) biosynthesis by human fetal lung fibroblasts IMR-90 (FLF), after 5 days of incubation by 7.4 +/- 1.4 times of the control level. Other phospholipid liposomes, such as phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylglycerol (PG), had no effect on t-PA biosynthesis by FLF. The induction of t-PA biosynthesis by PI liposomes was inhibited by specific inhibitors of phosphoinositide pathway: gentamycin and lithium chloride. Thus, gentamycin inhibited the effect of PI liposomes on t-PA biosynthesis by 76% (P less than 0.001), while it had no effect on control FLF. Likewise, lithium chloride inhibited t-PA biosynthesis of both PI-treated and control FLF by greater than 84%. The induction of t-PA biosynthesis by PI liposomes was dependent on RNA transcription and independent of DNA biosynthesis.
Floru
S
S
Department of Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Gelvan
A
A
Maran
R
R
Kadouri
A
A
Cohen
A M
AM
D016590:Aphidicolin; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004224:Diterpenes / Q000494:pharmacology; D004337:Drug Carriers; D005333:Fetus / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005839:Gentamicins / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008081:Liposomes; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000008:administration & dosage* / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D002712:Chlorides; D004224:Diterpenes; D004337:Drug Carriers; D005839:Gentamicins; D008081:Liposomes; D010716:Phosphatidylinositols; D016590:Aphidicolin; D012313:RNA; D004247:DNA; D008094:Lithium; D004257:DNA Polymerase II; D010959:Tissue Plasminogen Activator; D018021:Lithium Chloride; D006918:Hydroxyurea