AJP - Endocrinology and Metabolism, Vol 263, Issue 5 E958-E964, Copyright © 1992 by American Physiological Society
Regulation of protein synthesis by modulation of intracellular calcium in rat liver
S. R. Kimball and L. S. Jefferson
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033.
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)
