Search results for "eIF2 alpha"
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Between Scylla and Charibdis: eIF2α kinases as targets for cancer chemotherapy
2011
[EN] The eIF2 alpha kinases integrate translation initiation rates with nutrient availability, thus allowing cells to adapt to nutrient scarcity. Recent evidence has uncovered new functions of these kinases in tumour cell biology, ranging from regulation of cell cycle progression, maintenance of genome stability, control of apoptosis, and cell survival under nutrient stress and hypoxia. Accordingly, active eIF2 alpha kinases modulate the antineoplasic activity of several antitumour drugs, either by exacerbating their cytotoxic effect or by promoting chemoresistance. Understanding of eIF2 alpha kinases molecular roles may provide mechanistic insights into how tumour cells sense and adapt to …
Endoplasmic Reticulum Stress Inhibition Protects against Excitotoxic Neuronal Injury in the Rat Brain
2007
Elevated brain glutamate with activation of neuronal glutamate receptors accompanies neurological disorders, such as epilepsy and brain trauma. However, the mechanisms by which excitotoxicity triggers neuronal injury are not fully understood. We have studied the glutamate receptor agonist kainic acid (KA) inducing seizures and excitotoxic cell death. KA caused the disintegration of the endoplasmic reticulum (ER) membrane in hippocampal neurons and ER stress with the activation of the ER proteins Bip, Chop, and caspase-12. Salubrinal, inhibiting eIF2α (eukaryotic translation initiation factor 2 subunit α) dephosphorylation, significantly reduced KA-induced ER stress and neuronal deathin vivo…