| Autor: |
Yoshikawa, Akifumi, Kamide, Tomoya, Hashida, Koji, Ta, Hieu Minh, Inahata, Yuki, Takarada‐Iemata, Mika, Hattori, Tsuyoshi, Mori, Kazutoshi, Takahashi, Ryosuke, Matsuyama, Tomohiro, Hayashi, Yutaka, Kitao, Yasuko, Hori, Osamu |
| Předmět: |
|
| Zdroj: |
Journal of Neurochemistry; Feb2015, Vol. 132 Issue 3, p342-353, 12p |
| Abstrakt: |
To dissect the role of endoplasmic reticulum (ER) stress and unfolded protein response in brain ischemia, we investigated the relevance of activating transcription factor 6α (ATF6α), a master transcriptional factor in the unfolded protein response, after permanent middle cerebral artery occlusion (MCAO) in mice. Enhanced expression of glucose-regulated protein78, a downstream molecular chaperone of ATF6α, was observed in both neurons and glia in the peri-infarct region of wild-type mice after MCAO. Analysis using wild-type and Atf6α −/− mice revealed a larger infarct volume and increased cell death in the peri-ischemic region of Atf6α −/− mice 5 days after MCAO. These phenotypes in Atf6α −/− mice were associated with reduced levels of astroglial activation/glial scar formation, and a spread of tissue damage into the non-infarct area. Further analysis in mice and cultured astrocytes revealed that signal transducer and activator of transcription 3 (STAT3)-glial fibrillary acidic protein signaling were diminished in Atf6α−/− astrocytes. A chemical chaperone, 4-phenylbutyrate, restored STAT3-glial fibrillary acidic protein signaling, while ER stressors, such as tunicamycin and thapsigargin, almost completely abolished signaling in cultured astrocytes. Furthermore, ER stress-induced deactivation of STAT3 was mediated, at least in part, by the ER stress-responsive tyrosine phosphatase, TC-PTP/PTPN2. These results suggest that ER stress plays critical roles in determining the level of astroglial activation and neuronal survival after brain ischemia. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Plný text