cAMP inhibits IGF-I-induced mitogenesis in fetal rat brown adipocytes: role of p21 ras.
Dibutyryl cAMP (DBcAMP) inhibited insulin-like growth factor I (IGF-I)-induced DNA synthesis of rat fetal brown adipocyte primary cultures. Its mitogenic inhibitory capacity, measured as [3H]thymidine incorporation into acid-precipitable material, was dose-dependent, being maximal at 0.5 mM. The entry of cells into S + G2/M phases of the cell cycle and the increase in cell number induced by IGF-I were partially inhibited by DBcAMP at 24 h and totally prevented at 48 h. DBcAMP inhibited the mRNA expression of c-myc induced by IGF-I at 2 h. Moreover, DBcAMP inhibited in parallel H-ras mRNA expression, p21 ras, and proliferating cellular nuclear antigen protein content induced by IGF-I at 24 and 48 h of culture, respectively, suggesting the involvement of p21 ras in the progression of fetal brown adipocytes through the S phase of the cell cycle and DNA synthesis.
Valverde
A M
AM
Departamento de Bioquímica y Biología Molecular, Centro Mixto CSIC/UCM, Facultad de Farmacia, Ciudad Universitaria, Madrid, Spain.
Lorenzo
M
M
Teruel
T
T
Benito
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism*; D005333:Fetus; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc; D011905:Genes, ras; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D016895:Culture Media, Serum-Free; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D003994:Bucladesine; D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP; D016283:Proto-Oncogene Proteins p21(ras); D015056:1-Methyl-3-isobutylxanthine