https://scholars.lib.ntu.edu.tw/handle/123456789/563358
標題: | C/EBP homologous protein (CHOP) deficiency aggravates hippocampal cell apoptosis and impairs memory performance | 作者: | CHANG-MU CHEN Wu C.-T. CHIH-KANG CHIANG Liao B.-W. Liu S.-H. |
公開日期: | 2012 | 卷: | 7 | 期: | 7 | 來源出版物: | PLoS ONE | 摘要: | Neurodegenerative disorders are growing burdens in modern societies because of increased life expectancy. Most neurodegenerative disorders commonly possess a similar neuropathological feature - the accumulation of abnormal protein aggregates or inclusions (misfolded proteins) in the brain. One of the main functions of endoplasmic reticulum (ER) is to initiate proper protein folding to facilitate protein secretion through the induction of unfolded protein response (UPR). C/EBP homologous protein (CHOP) induction has been demonstrated to be a signaling event underlying ER stress-induced cell apoptosis. In this study, we explored the role of CHOP in the hippocampal cell apoptosis and memory performance injury under an induced ER stress condition. Adult male wild type (C57BL/6J) and CHOP knockout (CHOP-/-) mice were intracerebroventricularly injected with tunicamycin. Tunicamycin can induce ER stress and cell apoptosis in mouse hippocampus. Compared with wild type mice, CHOP-/- mice showed an enhanced hippocampal cell apoptosis, worse performance in memory-related behavioral tests, and attenuated IRE-1 expression under tunicamycin treatment. The aggravated cell apoptosis and worse memory performance in CHOP-/- mice might be due to the deficiency of CHOP protein resulted in the impaired adaptive/pathological transcriptional response, the decreased IRE-1 and XBP-1 expressions, and the increased JNK phosphorylation to cope with ER stress. Taken together, these results suggest that CHOP may play a protective role in the hippocampal cell apoptosis and impairment of memory performance. ? 2012 Chen et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864008957&doi=10.1371%2fjournal.pone.0040801&partnerID=40&md5=4a89655b09a030713e354af9bcb3897a https://scholars.lib.ntu.edu.tw/handle/123456789/563358 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0040801 | SDG/關鍵字: | growth arrest and DNA damage inducible protein 153; inositol requiring kinase 1; protein; stress activated protein kinase; tunicamycin; unclassified drug; X box binding protein 1; animal behavior; animal cell; animal experiment; animal model; apoptosis; article; brain cell; brain function; controlled study; disease exacerbation; endoplasmic reticulum stress; enzyme phosphorylation; hippocampus; male; memory disorder; mouse; neuroprotection; nonhuman; protein deficiency; protein expression; protein function; Animals; Apoptosis; Behavior, Animal; Caspase 12; Caspase 9; Cell Survival; Endoplasmic Reticulum Stress; Gene Expression Regulation; Heat-Shock Proteins; Hippocampus; Male; Memory; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons; Transcription Factor CHOP; Tunicamycin; Mus |
顯示於: | 毒理學研究所 |
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