Inhibitory effect of cyclosporin A peptide on rat hepatocytes proliferation induced by mitogens.
Treatment of cultured rat hepatocytes with cyclosporin A (0.01-1 microM) for 24, 48, or 72 h in the presence of insulin and epidermal growth factor induced an inhibition on cell proliferation in a time- and concentration-dependent manner, with an IC50 = 0.05 microM CsA corresponding to 48-h treatment. The inhibitory effect of CsA at < or = 0.1 microM doses for 48 h on [3H]thymidine uptake was reversed after withdrawal of the drug and subsequent addition of insulin plus EGF or serum; however, at 1 microM CsA the effect was irreversible and numerous bright small vesicles were observed. The molecular mechanism involved in CsA action in hepatocytes seems to be independent on cAMP and pertussis-toxin sensitive G proteins.
Rodriguez-Henche
N
N
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares, Spain.
Román
I D
ID
Fueyo
J
J
Menor
C
C
Zueco
J A
JA
Prieto
J C
JC
Guijarro
L G
LG
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry*; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology*; D008297:Male; D008934:Mitogens / Q000037:antagonists & inhibitors; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007328:Insulin; D008934:Mitogens; D010455:Peptides; D010566:Virulence Factors, Bordetella; D004815:Epidermal Growth Factor; D016572:Cyclosporine; D004247:DNA; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins