Effects of polyamine levels on the degradation of short-lived and long-lived proteins in cultured L-132 human lung cells.
Biogenic polyamines have important regulatory functions in various biological processes and it has also been suggested that they could modulate intracellular protein degradation. For an overall assessment of the role of polyamines in this process, we have investigated the effect that the decrease in intracellular polyamine levels caused by inhibitors of polyamine biosynthesis brings about on the degradation of the pools of short- and long-lived proteins in cultured L-132 human lung cells. Treatment of cells with 100 microM (2R,5R)-delta-methyl acetylenic putrescine (MAP), a potent enzyme-activated irreversible inhibitor of ornithine decarboxylase, or with 100 microM MAP plus 50 microM N-butyl 1,3-diaminopropane, a specific inhibitor of spermine synthase, caused a similar decrease (65-70% of control) in the total intracellular levels of polyamines, although they affected the concentrations of spermidine and spermine differently. The effect of the two treatments on protein degradation was essentially the same. In polyamine-depleted cells we observed an inhibition of degradation in long-lived proteins of 16% (P<0.05), with a significant increase in the half-life (t12) of this pool from 100.5 to 120.1 h. This was concomitant with an increase of 26% (P<0. 05) in degradation in short-lived proteins, with a significant decrease in the t12 of this pool from 0.85 to 0.67 h. Recovery of polyamine levels by the addition of 50 microM spermidine to polyamine-depleted cells resulted in a restoration of the degradation rates in both pools of proteins. The way(s) by which polyamines could modulate proteolysis are discussed.
Corella
D
D
Instituto de Investigaciones Citológicas, Fundación Valenciana de Investigaciones Biomédicas, Amadeo de Saboya, 4, 46010-Valencia, Spain.
Guillén
M
M
Hernández
J M
JM
Hernández-Yago
J
J
D000480:Alkynes; D002460:Cell Line; D003959:Diamines / Q000494:pharmacology*; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D008962:Models, Theoretical; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D013097:Spermine Synthase / Q000037:antagonists & inhibitors; D013462:Sulfur Radioisotopes
D000480:Alkynes; D003959:Diamines; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011506:Proteins; D013462:Sulfur Radioisotopes; C058695:N-butyl-1,3-diaminopropane; C039613:6-heptyne-2,5-diamine; D008715:Methionine; D013097:Spermine Synthase; D000518:Eflornithine