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Inhibition of reticulocyte lysate protein synthesis by heavy metal ions involves eIF-2. cap alpha. phosphorylation

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5897958
; ;

Heavy metal ions inhibit protein synthesis and disaggregate polyribosomes in several tissues and cell types. They have initiated studies to determine the mechanism by which this inhibition occurs utilizing the hemin-supplemented rabbit reticulocyte lysate as a model system. The inhibition of protein synthesis observed in the presence of heavy metal ions occurs with biphasic kinetics in a concentration dependent manner, which correlates with the biological toxicity of the ion. Highly toxic ions (AsO/sub 2//sup -/, Cd/sup + +/, Hg/sup + +/, Pb/sup + +/) inhibit protein synthesis by 50% at concentrations of 5-10 ..mu..M. In comparison, Cu/sup + +/, Fe/sup + +/, Zn/sup + +/ and GSSG inhibited protein synthesis by 50% at concentrations of 60, 250, 300 and 350 ..mu..M, respectively. The inhibition of protein synthesis was accompanied by the phosphorylation of eIF-2..cap alpha.., and was reversed or prevented by the addition of 1 mM DTT, 10 mM cAMP, 2 mM MgGTP, eIF-2 or the reversing factor (RF). Glucose-6-phosphate was found to have no effect. The data indicate that the inhibition of protein synthesis observed with the addition of heavy metal ions to reticulocyte lysates is due to the phosphorylation of eIF-2..cap alpha...

Research Organization:
Oklahoma State Univ., Stillwater
OSTI ID:
5897958
Report Number(s):
CONF-870644-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 46:6; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ARSENIC
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY FLUIDS
CADMIUM
CHEMICAL REACTIONS
COPPER
DOSE-RESPONSE RELATIONSHIPS
ELEMENTS
ERYTHROCYTES
INHIBITION
IRON
LEAD
MAMMALS
MATERIALS
MERCURY
METALS
ORGANIC COMPOUNDS
PHOSPHORYLATION
PROTEINS
RABBITS
RETICULOCYTES
SEMIMETALS
SYNTHESIS
TOXICITY
TRANSITION ELEMENTS
VERTEBRATES
ZINC