Possible involvement of pertussis toxin-sensitive GTP-binding protein(s) in c-fos expression during differentiation of 3T3-L1 fibroblasts to adipocytes.
Following the differentiation of 3T3-L1 fibroblasts by insulin/dexamethasone/methylisobutylxanthine, marked increases in cAMP levels by isoproterenol but not forskolin and in 2-deoxyglucose uptake by insulin occurred. Pertussis toxin-pretreatment prior to addition of insulin/dexamethasone/methylisobutylxanthine and exposure of cells to pertussis toxin during differentiation attenuated glycerophosphate dehydrogenase activity as a differentiation marker enzyme and the responses to isoproterenol and insulin by approximately 50% of those in pertussis toxin-untreated cells. On the other hand, insulin/dexamethasone/methylisobutylxanthine caused induction of c-fos proto-oncogene in confluent 3T3-L1 fibroblasts. This induction was also reduced in pertussis toxin-pretreated cells. These results suggested that pertussis toxin-sensitive GTP-binding protein(s) is involved in expression of c-fos mRNA accompanied by differentiation. In addition, accumulation of c-fos mRNA by insulin/dexamethasone/methylisobutylxanthine was enhanced in protein kinase C-depleted cells pretreated with phorbol 12-myristate 13-acetate, indicating that protein kinase C may negatively regulate c-fos expression induced by insulin/dexamethasone/methylisobutylxanthine.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
T
T
Uehara
T
T
Chihara
Y
Y
Tokumitsu
Y
Y
Nomura
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D037342:Pertussis Toxin; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes; D012313:RNA / Q000032:analysis; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D007328:Insulin; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D012313:RNA; D003907:Dexamethasone; D003847:Deoxyglucose; D000242:Cyclic AMP; D005993:Glycerolphosphate Dehydrogenase; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine