Modulation of DNA synthesis in cultured muscle cells by 1,25-dihydroxyvitamin D-3.
Biphasic effects of 1,25-dihydroxyvitamin D-3 on DNA synthesis were shown in primary cultured (24 h) chick embryo myoblasts exposed to physiological concentrations of the hormone. The sterol stimulated [3H]thymidine incorporation into DNA in proliferating myoblasts, e.g., at early stages of culture prior to cell fusion or in high serum-treated cells. The opposite effects were observed during the subsequent stage of myoblast differentiation in low-serum media. The mitogenic effect of 1,25-dihydroxyvitamin D-3 was correlated with an increase in c-myc mRNA and a decrease in c-fos mRNA levels, whereas its inhibitory action on DNA synthesis was accompanied by increased myofibrillar and microsomal protein synthesis and an elevation of creatine kinase activity, the latter suggesting a stimulation of muscle cell differentiation by the sterol. These data are in agreement with the results of previous morphological studies. Treatment of myoblasts with the calcium ionophore X-537 A or the phorbol ester TPA caused only a transient stimulation of [3H]thymidine incorporation into DNA, which occurred earlier than the response elicited by 1,25-dihydroxyvitamin D-3, suggesting that changes in intracellular Ca2+ and kinase C activity are not major mediators of the hormone effects. A similar temporal profile of changes in calmodulin mRNA levels as that of [3H]thymidine incorporation into DNA was observed after treatment of myoblasts with the sterol, in accordance with the role of calmodulin in the regulation of cell proliferation. 1,25-dihydroxyvitamin D-3 may play a function in embryonic muscle growth and differentiation.
Drittanti
L
L
Departamento de Biología, Universidad Nacional del Sur, Bahía Blanca, Argentina.
de Boland
A R
AR
Boland
R
R
D000818:Animals; D001769:Blood; D002117:Calcitriol / Q000494:pharmacology*; D002147:Calmodulin / Q000235:genetics; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D002642:Chick Embryo; D004247:DNA / Q000096:biosynthesis*; D007832:Lasalocid / Q000494:pharmacology; D009124:Muscle Proteins / Q000096:biosynthesis; D009132:Muscles / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002147:Calmodulin; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D004247:DNA; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate; D007832:Lasalocid