Summary
The putrescine, spermidine, and spermine content of subcultured human newborn foreskin keratinocytes was determined during growth and early plateau phase and found to be highest during growth. Exposure of the cells to methylglyoxal bis(guanylhydrazone) during growth phase caused a dose-dependent fall in intracellular spermidine and spermine levels and an increase in putrescine levels at higher concentrations. These effects reflect inhibition of S-adenosyl methionine decarboxylase by the drug. At 8×10-6 M the drug reduced incorporation of leucine into protein, lowered or stopped the accumulation of DNA per dish, inhibited mitotic activity, and increased the histidine/leucine incorporation into protein. The last effect is regarded as induction of keratinization. All these effects were reversible if the use of the drug was discontinued after 3 days. Inhibition of the enzymes of polyamine biosynthesis may have value in psoriasis therapy.
Zusammenfassung
Der Putrescin-, Spermidin- und Spermingehalt in Subkulturen von menschlichen Vorhaut-Keratinocyten wurde während der Phase des schnellen Wachstums und der frühen Plateau-Phase bestimmt. Der höchste Wert wurde in der Wachstums-Phase gefunden. Zugabe von Methylglyoxal bis(guanylhydrazone) während der Wachstums-Phase resultierte in einer konzentrationsabhängigen Abnahme des intracellulären Spermidin- und Spermingehaltes und bei hoher Konzentration Zunahme des Putrescingehaltes. Diese Wirkungen reflektieren die Hemmung der S-adenosyl methionine Decarboxylase durch Methylglyoxal bis(guanylhydrazone). Eine Konzentration dieser Substanz von 8×10-6 M reduzierte den Einbau von radioaktivem Leucin in Eiweiß, reduzierte oder verhinderte die Ansammlung von DNA per Petrischale, inhibierte die mitotische Aktivität und erhöhte den Histidin/Leucin Einbau in Eiweiß. Letztere Wirkung wird als Induzierung der Epithelisierung angesehen. Alle diese Wirkungen waren reversibel, wenn die Inhibitor-Substanz nach 3 Tagen abgewaschen wurde. Hemmung der Enzyme der Polyamin Biosynthese können möglicherweise in der Psoriasistherapie wertvoll sein.
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This work was performed during the tenure of a Society for Investigative Dermatology Fellowship (to M.S.P.).
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Proctor, M.S., Liu, S.C.C. & Wilkinson, D.I. Effect of methylglyoxal bisguanylhydrazone on polyamine biosynthesis, growth, and differentiation of cultured keratinocytes. Arch Dermatol Res 269, 61–68 (1980). https://doi.org/10.1007/BF00404458
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DOI: https://doi.org/10.1007/BF00404458