Pravastatin, a HMG-CoA reductase inhibitor, blocks the cell cycle progression but not Ca2+ influx induced by IGF-I in FRTL-5 cells.
IGF-I, when added to the TSH-primed FRTL-5 cells, induces a long lasting Ca2+ influx, and then, DNA synthesis. Moreover, Ca2+ channel agonist, B AY K8644 can mimic these effects on cell proliferation. We studied the effect of HMG-CoA reductase inhibitor, Pravastatin on IGF-I-induced cell cycle progression in FRTL-5 cells. Pravastatin inhibited DNA synthesis induced both by IGF-I and by BAY K8644. In contrast, Ca2+ influx stimulated by IGF-I was unaffected. These data demonstrate that the signal transduction pathway evoked by IGF-I may possibly involve pravastatin-sensitive process at the downstream step of Ca2+ entry. HMG-CoA reductase inhibitors are known to modulate some cellular signal transduction systems by blocking the membrane attachment of low molecular weight GTP binding proteins such as p21ras. Therefore, pravastatin-sensitive process that we have shown here might possibly involve some of such small G protein.
Tada
H
H
Department of Laboratory Medicine, Osaka University School of Medicine, Japan.
Takada
K
K
Amino
N
N
Miyai
K
K
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D009281:Naphthalenes / Q000494:pharmacology*; D017035:Pravastatin; D051381:Rats; D013961:Thyroid Gland; D013972:Thyrotropin / Q000494:pharmacology
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D003994:Bucladesine; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D017035:Pravastatin; D002118:Calcium