Inhibition of microsomal calcium sequestration causes an impairment of initiation of protein synthesis in perfused rat liver.
The present study examined the effect of 2,5-di-(tert-butyl)-hydroquinone (tBuHQ), an inhibitor of liver microsomal calcium sequestration, on initiation of protein synthesis in perfused rat liver. Perfusion of livers with a concentration of tBuHQ previously shown to completely inhibit microsomal calcium sequestration in isolated hepatocytes caused a 50% inhibition of protein synthesis. The inhibition was characterized by an increase in liver content of free ribosomal particles and a decrease in polysomes indicating that peptide-chain initiation was slowed relative to elongation. Furthermore, the inhibition was associated with a 7.5-fold increase in the proportion of the alpha-subunit of eukaryotic initiation factor 2 (eIF-2) present in the phosphorylated form and a reduction in the activity of eukaryotic initiation factor 2B (eIF-2B) to 37% of the control value. The results suggest that protein synthesis in rat liver is regulated directly by changes in intracellular calcium concentration through a mechanism involving modulation of the phosphorylation state of eIF-2 alpha.
Kimball
S R
SR
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey Medical Center 17033.
Jefferson
L S
LS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D006873:Hydroquinones / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D015852:Eukaryotic Initiation Factor-2; D006873:Hydroquinones; D011500:Protein Synthesis Inhibitors; C018855:2-tert-butylhydroquinone; D002118:Calcium