Regulation of protein synthesis by modulation of intracellular calcium in rat liver.
The rate of protein synthesis can be modulated in intact cells by varying the concentration and subcellular distribution of intracellular calcium. Because the biochemical reactions required for the pathway of protein synthesis occur in the cytosol of the cell, it might be expected that protein synthesis would be controlled by free cytosolic calcium rather than the sequestered cation. However, a recent report proposed that maintenance of optimal rates of protein synthesis depends on the amount of calcium sequestered in the endoplasmic reticulum rather than free cytosolic calcium (C.O. Brostrom and M. A. Brostrom, Annu. Rev. Physiol. 52: 577-590, 1990). In the present study, rat livers were perfused with buffer containing various compounds previously shown to alter intracellular calcium concentration and distribution in isolated cells. It was found that conditions designed to cause a rise in free cytosolic calcium had no effect on protein synthesis. In contrast, conditions designed to cause depletion of sequestered calcium resulted in an inhibition of protein synthesis characterized by a reduction in peptide-chain initiation relative to elongation. The inhibition of protein synthesis was further localized to a decrease in the activity of eukaryotic initiation factor (eIF) 2B as measured in extracts from perfused livers. The inhibition of eIF-2B activity was associated with a 2.4-fold increase in the proportion of the alpha-subunit of eIF-2 in the phosphorylated form. In summary, the results of the present study support a model whereby mobilization of calcium sequestered in the endoplasmic reticulum results in an inhibition of protein synthesis in rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Kimball
S R
SR
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033.
Jefferson
L S
LS
D000818:Animals; D019703:Calcineurin; D002118:Calcium / Q000172:deficiency / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010448:Peptide Initiation Factors / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000494:pharmacology; D019892:eIF-2 Kinase
D002148:Calmodulin-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; D010448:Peptide Initiation Factors; D014667:Vasopressins; D004533:Egtazic Acid; D011494:Protein Kinases; D019892:eIF-2 Kinase; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D002118:Calcium