The role of polyamines in somatomedin‐stimulated differentiation of L6 myoblasts

Ewton, Daina Z.; Erwin, Bradley G.; Pegg, Anthony E.

doi:10.1002/jcp.1041200302

Cited by 51 publications

(12 citation statements)

References 32 publications

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“…1B). A similar decline in ODCase activity has been reported previously, after fusion of the rat L6 muscle cell line (8,41) and after withdrawal of a variety of cell types from the cell cycle in response to mitogen depletion (34). This rapid decrease in ODCase activity suggests that ODCase synthesis is blocked when cells withdraw from the cell cycle.…”

supporting

confidence: 84%

“…Myogenesis is accompanied by the expression of a variety of musclespecific gene products involved in the specialized functions of the myofiber (25). During this time period, some genes encoding proteins associated with cell proliferation are down-regulated (8,26,32,41). Among the proteins that are deinduced during muscle differentiation is ornithine decarboxylase (ODCase), the rate-limiting enzyme in polyamine biosynthesis.…”

mentioning

confidence: 99%

“…Among the proteins that are deinduced during muscle differentiation is ornithine decarboxylase (ODCase), the rate-limiting enzyme in polyamine biosynthesis. Previous studies have shown that ODCase activity decreases dramatically at the time of myoblast fusion, suggesting that the down-regulation of this enzyme may play a central role in control of the onset of differentiation (8,41). In addition to its regulation during muscle development, ODCase has been shown to be rapidly induced in quiescent cells by a variety of hormones and growth factors (for review, see reference 34).…”

mentioning

confidence: 99%

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Mitogens and protein synthesis inhibitors induce ornithine decarboxylase gene transcription through separate mechanisms in the BC3H1 muscle cell line.

Olson¹,

Spizz²

1986

Mol. Cell. Biol.

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Ornithine decarboxylase (ODCase), the rate-limiting enzyme in polyamine biosynthesis, exhibits dramatic fluctuations in activity in response to a variety of hormones and growth factors and has been shown to be down-regulated during myogenesis. In the present study, the molecular mechanisms involved in expression of ODCase mRNA were examined in cells of the BC3H1 muscle line. Proliferating, undifferentiated Skeletal muscle differentiation involves the withdrawal of proliferating myoblasts from the cell cycle and their subsequent fusion to form multinucleated myotubes. Myogenesis is accompanied by the expression of a variety of musclespecific gene products involved in the specialized functions of the myofiber (25). During this time period, some genes encoding proteins associated with cell proliferation are down-regulated (8,26,32,41). Among the proteins that are deinduced during muscle differentiation is ornithine decarboxylase (ODCase), the rate-limiting enzyme in polyamine biosynthesis. Previous studies have shown that ODCase activity decreases dramatically at the time of myoblast fusion, suggesting that the down-regulation of this enzyme may play a central role in control of the onset of differentiation (8,41). In addition to its regulation during muscle development, ODCase has been shown to be rapidly induced in quiescent cells by a variety of hormones and growth factors (for review, see reference 34). ODCase is also regulated in a cell cycle-specific manner, with large increases in enzyme activity being required for progression of cells from the G1 to the S phase of the cell cycle (34). Despite the apparent importance of ODCase in the control of cell proliferation and possibly differentiation, the molecular mechanisms involved in regulation of ODCase gene expression remain to be determined.The BC3H1 nonfusing muscle cell line has been used as a model to study certain aspects of both smooth-muscle and skeletal-muscle differentiation (29-31, 35, 42 rapidly and do not express the muscle phenotype (20,(29)(30)(31). The removal of serum from the culture media results in the withdrawal of cells from the cell cycle and the induction of a variety of muscle-specific gene products. The accumulation of muscle-specific mRNAs can be rapidly reversed by reexposure of quiescent differentiated cells to serum (29,30) or to fibroblast growth factor (G. Spizz, D. Roman, A. Strauss, and E. Olson, J. Biol. Chem., in press).Previously, Olson et al. (30) reported that an mRNA encoding a polypeptide of Mr -50,000 was preferentially expressed in undifferentiated BC3H1 cells and was downregulated during differentiation. Because of its Mr and pattern of regulation, we considered the possibility that this mRNA might encode ODCase. In the present study, we have analyzed the molecular mechanisms involved in the regulation of ODCase mRNA expression during differentiation of BC3H1 cells. ODCase mRNA was expressed at relatively high levels in proliferating undifferentiated cells in media with 20% serum.

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confidence: 84%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Mitogens and protein synthesis inhibitors induce ornithine decarboxylase gene transcription through separate mechanisms in the BC3H1 muscle cell line.

Olson¹,

Spizz²

1986

Mol. Cell. Biol.

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“…Although Figures 3 and 4 indicate that IFN does not inhibit differentiation of this cell line by such a mechanism, such a conclusion must be made with caution, because 1) we were unable to assay intracellular polyamine levels on the small numbers of cells available in these experiments and 2) our ODC assays were performed 16 hr after the last medium change, possibly failing to detect any effects of IFN on serum-induced increases in ODC. A requirement for polyamines has been demonstrated for the differentiation of several cell types, including L6 myoblasts (Ewton et al, 1984). Thus the potentiation of differentiation of the MM14DZ cell line by polyamines might be related to their essential role in myogenesis.…”

Section: Discussionmentioning

confidence: 98%

Interferon‐mediated inhibition of differentiation in a murine myoblast cell line

Multhauf

Lough

1986

Journal Cellular Physiology

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The effects of highly purified (greater than 5 X 10(7) IU/mg) murine beta-interferon (IFN) on a mouse myoblast line (MM14DZ) have been investigated to confirm and extend the previous observation that partially purified chicken interferon inhibits differentiation of cultured avian myoblasts (Lough et al., Biochem Biophys Res Commun 109:92, 1982). Cultures treated with 20-2,000 lU IFN/ml medium for 5 days exhibited dose-dependent 1) inhibition of differentiation, as indicated by reduced myotube formation and creatine kinase (CK) activity and 2) increases in DNA content, suggesting that the inhibitory effect was accompanied by continued proliferation of myoblasts. Mock-IFN had no such effects. Based on findings in other systems that IFN inhibits activity of ornithine decarboxylase (ODC), the polyamine products of which are required for myogenesis, the hypothesis that inhibition of differentiation was mediated by an effect of IFN on polyamine metabolism was tested. However, observations that 1) IFN-treated myoblasts retained control levels of ODC activity and 2) exogenous polyamines did not prevent IFN-inhibition did not indicate such a mechanism of action. On the other hand, treatment of control cultures with polyamines alone resulted in potentiation of myogenesis as revealed by precocious myotube formation and a marked increase in CK activity.

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“…Experiments conducted in animal and cell culture in non-hematologic cell types have also yielded differing results regarding the role of changes in cellular polyamine levels in the differentiation process. In some cell types, such as leukemic myeloblasts [6,11,12], cartilage [34], chondrocytes [35], and myoblasts [36] differentiation is accompanied by an increase in cellular ODC activity and polyamine levels. DFMO has been found to inhibit DMSOinduced differentiation of murine erythroleukemia [11], matrix-induced development of cartilage and bone [34], somatomedin-induced differentiation of L-6-myoblast [36,37], 3T3-L1 preadipocyte differentiation [38], rabbit chondrocyte differentiation [35], and the processes of intestinal maturation [39] and germ cell differentiation and embryonic development [40,41].…”

Section: Discussionmentioning

confidence: 99%

Mononuclear cell polyamine content associated with myeloid maturation in patients with leukemia during administration of polyamine inhibitors

et al. 1989

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Fourteen patients with acute leukemia in relapse were treated with difluoromethylornithine (DFMO) alone or in combination with methylglyoxal-bis(guanylhydrazone) (MGBG) as part of Phase I studies. Five patients included in the trial exhibited morphologic evidence of cellular differentiation during the course of treatment. In one patient who exhibited no blasts and a normal white blood cell differential at the end of treatment the mononuclear cell content of all three polyamines declined after an initial increase in spermidine and spermine content. In the other patients in whom the cellular maturation was less pronounced the mononuclear cell polyamine levels remained stable or increased over the treatment time. No absolute difference was apparent between the cellular polyamine levels detected in patients at the times of the greatest increase in per cent circulating neutrophils as compared to the cellular levels present in patients whose circulating mononuclear cell number were increasing. Circulating mononuclear cell putrescine, spermidine, and spermine levels varied over two orders of magnitude from patient to patient and the range of values detected in each state completely overlapped those present in the other. It does not appear from the present study that there is a consistent human leukemic cell polyamine content at which cellular differentiation occurs.

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The role of polyamines in somatomedin‐stimulated differentiation of L6 myoblasts

Cited by 51 publications

References 32 publications

Mitogens and protein synthesis inhibitors induce ornithine decarboxylase gene transcription through separate mechanisms in the BC3H1 muscle cell line.

Mitogens and protein synthesis inhibitors induce ornithine decarboxylase gene transcription through separate mechanisms in the BC3H1 muscle cell line.

Interferon‐mediated inhibition of differentiation in a murine myoblast cell line

Mononuclear cell polyamine content associated with myeloid maturation in patients with leukemia during administration of polyamine inhibitors

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