| First Author | Osada N | Year | 2009 |
| Journal | Neurochem Int | Volume | 54 |
| Issue | 7 | Pages | 403-9 |
| PubMed ID | 19428781 | Mgi Jnum | J:150590 |
| Mgi Id | MGI:3851049 | Doi | 10.1016/j.neuint.2009.01.010 |
| Citation | Osada N, et al. (2009) Apolipoprotein E-deficient mice are more vulnerable to ER stress after transient forebrain ischemia. Neurochem Int 54(7):403-9 |
| abstractText | Apolipoprotein E-deficient (apoE(-/-)) mice have been shown to have increased vulnerability to neuronal damage induced by cerebral ischemia; however, the mechanism of this increased vulnerability remains unclear. In order to define the role of the apoE protein against ischemia-induced ER stress and cell death, experiments were performed to compare ER stress-associated chaperones and signal proteins in the hippocampus of apoE(-/-) mice to those of WT mice after being subjected to forebrain ischemia and reperfusion. Although neuronal loss in area CA1-CA3 of the hippocampus was observed 3 days after ischemia in both types of mice, the damage in apoE(-/-) mice was more severe. In apoE(-/-) mice, a more extensive increase in 78-kDa glucose-regulated protein (GRP78) was observed after the insult, whereas the level of GRP94 was not changed. The expression of both C/EBP homologous protein (CHOP) and caspase-12 was increased in the hippocampus in both WT and apoE(-/-) mice after ischemia. The increased levels of CHOP in apoE(-/-) mice were significantly higher than those in WT mice, whereas the levels of caspase-12 in the two were comparable. Furthermore, whereas the levels of c-Jun N-terminal kinase (JNK), p-JNK1 and p-JNK2 in WT mice were unchanged after ischemia, they were significantly increased in apoE(-/-) mice 24h and 48h after ischemia. These results suggest that increased vulnerability of the hippocampus to forebrain ischemia and reperfusion in apoE(-/-) mice is at least partly attributable to perturbed induction of an ER chaperone, GRP 94, and enhancement of the CHOP- and JNK-dependent apoptotic pathway in the hippocampus. |
