| First Author | Stanciu M | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 6 | Pages | 4010-7 |
| PubMed ID | 11726647 | Mgi Jnum | J:74534 |
| Mgi Id | MGI:2158593 | Doi | 10.1074/jbc.M104479200 |
| Citation | Stanciu M, et al. (2002) Prolonged Nuclear Retention of Activated Extracellular Signal-regulated Protein Kinase Promotes Cell Death Generated by Oxidative Toxicity or Proteasome Inhibition in a Neuronal Cell Line. J Biol Chem 277(6):4010-7 |
| abstractText | In the HT22 mouse hippocampal cell line and primary immature embryonic rat cortical neurons, glutamate-induced oxidative toxicity is associated with a delayed but chronic activation of extracellular signal-regulated kinase-1/2 (ERK-1/2). ERK-1/2 is also activated in HT22 cells that undergo caspase-dependent cell death upon inhibition of proteasome-dependent protein degradation brought about by MG132 treatment. As in glutamate-treated HT22 cells and primary neurons, inhibition of MEK-1, an upstream activator of ERK-1/2 protects against MG132-induced toxicity. Furthermore, activated ERK-1/2 is retained within the nucleus in glutamate- and MG132-treated HT22 cells. Although previous studies suggested that ERK-1/2 activation was downstream of many cell death-inducing signals in HT22 cells, we show here that cycloheximide, the Z-vad caspase inhibitor, and a nonlethal heat shock protect against glutamate- and MG132-induced toxicity without diminishing ERK-1/2 activation. In these cases, ERK-1/2, although chronically activated, is not retained within the nucleus but accumulates within the cytoplasm. Thus, persistent nuclear retention of activated ERK-1/2 may be a critical factor in eliciting proapoptotic effects in neuronal cells subjected to oxidative stress or proteasome inhibition. |
