Glucocorticoids inhibit precursor incorporation into protein in splenic lymphocytes by stimulating protein degradation and expanding intracellular amino acid pools |
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Authors: | Richard G MacDonald John A Cidlowski |
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Institution: | Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405 U.S.A |
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Abstract: | In the presence of tracer concentrations of extracellular leucine (5 μM), treatment of rat splenic lymphocyte suspensions in vitro with 1 μM dexamethasone for 2.5–4 h caused a 30–35% inhibition of 3H]leucine incorporation into protein. As the extracellular leucine concentration was raised to 5 mM, this inhibition was progressively reduced to 0–12%. This phenomenon correlated with a marked dependence on extracellular leucine concentration of the dexamethasone-dependent enlargement of free intracellular leucine pools in splenic lymphocytes: a 123% increase in pool size with tracer extracellular leucine; a 10% increase with 5 mM leucine. Varying extracellular leucine had no effect on: (1) nuclear 3H]dexamethasone binding by the cells; (2) the concentration of dexamethasone needed for half-maximal inhibition of 3H]leucine incorporation; (3) the time course of onset and maximal expression of the hormonal inhibition of 3H]leucine incorporation; or (4) the magnitude of dexamethasone-dependent inhibition of 3H]uridine incorporation into RNA by these cells. There was no detectable effect of dexamethasone on uptake and retention of 3H]leucine by the cells, regardless of the extracellular leucine concentration. Treatment of splenic lymphocytes for 4 h in vitro with 1 μM dexamethasone caused a small shift of ribosomes from larger aggregate polysomes to smaller forms. Thus, glucocorticoid-induced inhibition of amino acid incorporation in splenic lymphocytes is a multicomponent response, of which an actual decrease in protein synthesis is only a small part. Enlargement of free intracellular amino acid pools, probably resulting from increased protein degradation, is the major contributing factor to the hormonal inhibition of amino acid incorporation. |
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Keywords: | Glucocorticoid Protein degradation Amino acid incorporation Amino acid pool (Spleen lymphocyte) |
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