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Genomics and proteomics
Author(s) -
Law, LP,
Chung, SSM,
Lo, ACY,
Chung, SK
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j..2003.0c3_1.x
Subject(s) - citation , computer science , proteomics , genomics , information retrieval , world wide web , library science , data science , biology , genetics , genome , gene
Induced endothelin-1(ET-1) expression was observed in astrocytes after experi-mental ischemic stroke, suggesting a potential role of astrocytic ET-1 in ischemicbrain injury. Previously, we showed that transgenic mice over-expressing ET-1 inastrocytes (GET mice) displayed increased cerebral infarct size and more severeneurological decits upon focal cerebral ischemia induced by middle cerebralartery occlusion (MCAO). However, the mechanism behind astrocytic ET-1 onischemia-induced brain injury was not clear. Here, expression prole of ET systemwas examined by real-time PCR analyses. In GET brain after MCAO ET-1 levelwas further increased while ET-3 level was lowered. ETA receptor level was up-regulated while ETB receptor level remained unchanged. After MCAO GET brainshowed lower occludin level and increased Evans blue extravasation, indicatingincreased blood–brain barrier (BBB) breakdown which correlated with our resultsthat GET mice displayed increased brain swelling and brain water content. Linearregression analysis also showed correlation of severity of infarction and brainswelling with neurological decit exacerbation. There was signicant p35 down-regulation after MCAO, suggesting involvement of p25/cdk5 cell death pathwayin increased infarct formation. Caspase9 expression was also increased. Theseresults suggested that increased astrocytic ET-1 resulted in BBB disruptionpossibly leading to increased formation of brain edema and swelling, infarct andneurological decits mediated through cdk5 pathway and, therefore, imposedadverse effects on brain injury after focal cerebral ischemia. Further globalscreening of ET-1-mediated signaling after MCAO will be discussed.Acknowledgements: Supported by RGC and UGC of Hong Kong (AoE/B-15/01).link_to_OA_fulltex