Assessment of p38 and extracellular signal-regulated kinase (ERK) in regulating apoptosis during low and high ER stress

The endoplasmic reticulum (ER) is an important organelle within the cell that has many functions including protein folding. When the protein folding capabilities of the ER are compromised ER stress occurs. Extracellular signal-regulated kinases (ERKs) and p38 are MAP kinases that are induced as a result of ER stress. ERK is a protein that has been associated with cell proliferation and survival while p38 is a protein that has been associated with apoptosis, which is programmed cell death. The objective of this study was to measure ERK and p38 induction over time during low and high ER stress. Another objective was to assess the roles of these MAP kinases as well as JNK, a kinase that has been associated with apoptotic signaling, in apoptosis. Using BHK-21 hamster fibroblast cells as the model cell line, neither ERK nor p38 induction was found to be time dependent. Induction of p38 was higher during high ER stress than for low ER stress, while ERK induction was not different during low and high stress. A cell death assay revealed that inhibition of p38 rescued cells up to moderately high ER stress, inhibition of ERK accelerated cell death, and JNK had no significant effect on cell death rate. Experiments to assess possible crosstalk between p38 and ERK during ER stress will be performed in the future