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Carbonyl cyanidep-trifluoromethoxyphenylhydrazone (FCCP) induces initiation factor 2α phosphorylation and translation inhibition in PC12 cells

Authors
Journal
FEBS Letters
0014-5793
Publisher
Wiley Blackwell (John Wiley & Sons)
Publication Date
Volume
492
Identifiers
DOI: 10.1016/s0014-5793(01)02247-5
Keywords
  • Calcium Ion
  • Initiation Factor 2 Kinase
  • Mitochondrion
  • Permeability Transition Pore
  • Pc12 Cell
  • Translation
Disciplines
  • Biology

Abstract

Abstract 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 α subunit of eIF2 (eIF2α) (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 eIF2α phosphatase were found. Translational regulation may play a significant role in the process triggered by mitochondrial calcium mobilization.

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