Feedback repression of polyamine uptake into mammalian cells requires active protein synthesis

• Published in: Biochemical and biophysical research communications Vol. 186; no. 1; pp. 81 - 88
• Main Authors: Mitchell, John L.A., Diveley, Roger R., Bareyal-Leyser, Aviva
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.07.1992; Elsevier
• Subjects: Animals; Biological and medical sciences; Biological Transport; Cell Line; Cell physiology; CHO Cells; Cricetinae; Cycloheximide - pharmacology; Feedback; Fundamental and applied biological sciences. Psychology; Kinetics; Liver Neoplasms, Experimental; Membrane and intracellular transports; Molecular and cellular biology; Polyamines - metabolism; Protein Biosynthesis; Puromycin - pharmacology; Spermidine - metabolism; Vertebrata; Polyamine; Mammalia; Cell line; Rat; Protein synthesis; Membrane transport; Spermidine; Rodentia; Protein synthesis inhibitor; Uptake; Hamster
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(05)80778-8

Two mammalian cell lines, rat hepatoma (HTC) and Chinese hamster ovary (CHO), were fed 10 to 50 μM spermidine while changes were monitored in intracellular polyamine levels and spermidine uptake activity. Normal feedback control preventing excessive polyamine uptake was found to be completely blocked by the addition of inhibitors of protein synthesis at the time of polyamine exposure. Under these conditions the cells accumulated abnormally high, toxic concentrations of spermidine. Further, continuous protein synthesis was needed to maintain repression of polyamine transporter proteins that had been inhibited previously by normal or elevated intracellular polyamines. These results suggest that a major factor in the regulation of polyamine uptake is the rapid, reversible inactivation of existing polyamine carrier molecules by an unstable protein whose synthesis is stimulated by intracellular polyamines.