Polyamine depletion inhibits the differentiation of L6 myoblast cells |
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Authors: | B G Erwin D Z Ewton J R Florini A E Pegg |
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Institution: | 1. Department of Physiology, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033 USA;2. Cancer Research Center, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033 USA;3. Biology Department, Syracuse University, Syracuse, NY 13210 USA |
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Abstract: | Exposure to alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, inhibited the insulin induced differentiation of L6 myoblast cells. Differentiation was assessed by measuring creatine kinase activity and by determining the percentage of nuclei in myotubes. The levels of putrescine and spermidine increased in stimulated cultures prior to their differentiation and these increases were blocked by alpha-difluoromethylornithine. Provision of exogenous putrescine was able to reverse the inhibitory effect of the drug. The anti-differentiative effect is observed only if alpha-difluoromethylornithine is added within twenty-four hours of insulin stimulation. In the experimental protocol used, alpha-difluoromethylornithine was added as the cultures approached confluence and had no effect on their ultimate DNA content. Therefore, the effect of alpha-difluoromethylornithine on myoblast differentiation is not secondary to an effect on cellular proliferation. These results indicate that polyamines may be involved in the mediation of muscle cell differentiation. |
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Keywords: | DMEM Dulbecco's modified Eagle's medium BSA bovine serum albumin DFMO α-difluoromethylornithine |
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