Premium
Eukaryotic Initiation Factor 4E Degradation During Brain Ischemia
Author(s) -
Neumar Robert W.,
DeGracia Donald J.,
White Blaine C.,
McDermott Paul J.,
Evans David R.,
Krause Gary S.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65031391.x
Subject(s) - ischemia , proteolysis , blot , eukaryotic initiation factor , phosphorylation , initiation factor , protein biosynthesis , translation (biology) , biology , messenger rna , chemistry , microbiology and biotechnology , biochemistry , medicine , enzyme , gene
Suppression of protein synthesis in the brain following an ischemic insult has been thought to occur because of inhibition of translation initiation. All eukaryotic mRNAs, with the exception of heat‐shock transcripts, require the activity of eukaryotic initiation factor (eIF) 4E for formation of the translation initiation complex, and eIF‐4E availability is rate‐limiting. The response of brain eIF‐4E concentration and phosphorylation following decapitation ischemia was studied in rat brain homogenates after electrophoresis and western blotting with antibodies against eIF‐4E and phosphoserine, respectively. There was no change in level of eIF‐4E after 5 min of ischemia ( p = 0.82 vs. time 0), but it had decreased 32 ( p = 0.01) and 57% ( p = 0.006) after 10 and 20 min of ischemia, respectively. There was no loss of serine phosphorylation on eIF‐4E beyond signal loss observed due to degradation of the protein itself ( p = 0.31). In vitro exposure of eIF‐4E to activated μ‐calpain resulted in a 50% loss in 10 min of eIF‐4E on western blots. If active eIF‐4E is required for translation of its own mRNA, degradation of this protein during ischemia, possibly by activated μ‐calpain, could be a direct mechanism of irreversible neuronal injury, and the rate of proteolysis of eIF‐4E could place an upper time limit on the maximal duration of global brain ischemia compatible with neurologic recovery.