Figure 11.

Proposed model of hypoxia/reoxygenation ER injury and protection. Motoneurons may be considered susceptible or resistant to injury from hypoxia/reoxygenation. Susceptible neurons have at baseline an unfolded protein response and activation of CHOP/GADD153, a proapoptotic protein. Under conditions of hypoxia/reoxygenation, CHOP/GADD153 is markedly increased and activated in susceptible motoneurons. This activation parallels an increase in activation of caspase-7 (ER specific) and caspase-3. In contrast, resistant motoneurons are able to phosphorylated eIF-2a and circumvent an activation of CHOP/GADD153 or caspases. Salubrinal, a specific protein phosphatase inhibitor, maintains phosphorylation of eIF-2a in susceptible motoneurons and converts the phenotype from susceptible to resistant to hypoxia/reoxygenation injury.