| First Author | Keller JN | Year | 2000 |
| Journal | J Cereb Blood Flow Metab | Volume | 20 |
| Issue | 10 | Pages | 1467-73 |
| PubMed ID | 11043909 | Mgi Jnum | J:133829 |
| Mgi Id | MGI:3784330 | Doi | 10.1097/00004647-200010000-00008 |
| Citation | Keller JN, et al. (2000) Oxidative stress-associated impairment of proteasome activity during ischemia-reperfusion injury. J Cereb Blood Flow Metab 20(10):1467-73 |
| abstractText | Numerous studies indicate a role for oxidative stress in the neuronal degeneration and cell death that occur during ischemia-reperfusion injury. Recent data suggest that inhibition of the proteasome may be a means by which oxidative stress mediates neuronal cell death. In the current study, the authors demonstrate that there is a time-dependent decrease in proteasome activity, which is not associated with decreased expression of proteasome subunits, after cerebral ischemia-reperfusion injury. To determine the role of oxidative stress in mediating proteasome inhibition, ischemia-reperfusion studies were conducted in mice that either overexpressed the antioxidant enzyme glutathione peroxidase [GPX 1(+)], or were devoid of glutathione peroxidase activity (GPX -/-). After ischemia-reperfusion, GPX 1(+) mice displayed decreased infarct size, attenuated neurologic impairment, and reduced levels of proteasome inhibition compared with either GPX -/- or wild type mice. In addition, GPX 1(+) mice displayed lower levels of 4-hydroxynonenal-modified proteasome subunits after ischemia-reperfusion injury. Together, these data indicate that proteasome inhibition occurs during cerebral ischemia-reperfusion injury and is mediated, at least in part, by oxidative stress. |
