Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) induces initiation factor 2 alpha phosphorylation and translation inhibition in PC12 cells.
We have investigated the effect of the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) on protein synthesis rate and initiation factor 2 (eIF2) phosphorylation in PC12 cells differentiated with nerve growth factor. FCCP treatment induced a very rapid 2-fold increase in intracellular Ca(2+) concentration that was accompanied by a strong protein synthesis rate inhibition (68%). The translation inhibition correlated with an increased phosphorylation of the alpha subunit of eIF2 (eIF2 alpha) (25% vs. 7%, for FCCP-treated and control cells, respectively) and a 1.7-fold increase in the double-stranded RNA-dependent protein kinase activity. No changes in the PKR endoplasmic reticulum-related kinase or eIF2 alpha phosphatase were found. Translational regulation may play a significant role in the process triggered by mitochondrial calcium mobilization.
Muñoz
F
F
Department of Biochemistry and Molecular Biology, Alcalà University, Madrid, Spain.
Martín
M E
ME
Salinas
M
M
Fando
J L
JL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology*; D002454:Cell Differentiation; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D014475:Uncoupling Agents / Q000494:pharmacology
D015852:Eukaryotic Initiation Factor-2; D014475:Uncoupling Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D020932:Nerve Growth Factor; D002118:Calcium