Insulin-Mediated Inhibition of Tyrosinase Activity and Protein Synthesis in Melanoma Cell Cultures
Ehlers, Susan Elizabeth
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Insulin lowers basal levels of tyrosinase activity and inhibits the MSH-stimulated rise in tyrosinase in Cloudman S-91 mouse melanoma cell cultures. These cultures are very sensitive to insulin. A concentration of insulin as low as 5 x 10 M insulin produces optimum inhibition. At maximum inhibition, tyrosinase activity is reduced to approximately 50% of control levels. Insulin inhibits cellular proliferation in melanoma cells; however, inhibition of tyrosinase activity precedes this effect. Insulin also inhibits the (Bu)2 cAMP and theophylline stimulated rise in enzyme activity. This finding suggests that insulin exerts its effects at a site distal to cAMP production. Insulin, in fact, does not lower cAMP levels in melanoma cells, nor does it alter the MSH-stimulated rise of cAMP. The inhibitory effect of insulin on tyrosinase activity could not be mimicked by either (Bu)2 cGMP or 8-bromo-cGMP, suggesting that insulin does not exert its effects by altering cellular levels of this nucleotide. Insulin decreases the incorporation of [3H]-leucine into trichloracetic acid insoluble material by 50%, an inhibition which corresponds well with the observed level of reduction of tyrosinase activity. This finding suggests that the inhibition of tyrosinase activity may be caused by a general reduction in protein synthesis due to insulin treatment.