期刊
CELL DEATH & DISEASE
卷 4, 期 -, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/cddis.2012.187
关键词
anthraquinone; brain; caspase; apoptosis; AKT; neuroprotective
类别
资金
- National Institutes of Health [NS070003]
- Laerdal Foundation for Acute Medicine
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R21NS070003] Funding Source: NIH RePORTER
Anthraquinone derivatives such as emodin have recently been shown to protect in models of beta amyloid beta (A beta) and tau aggregation-induced cell death. The mechanisms of action possibly involve preconditioning effects, anti-aggregation properties, and/or enhancing the phosphatidylinositol-3-kinase (PI3K)/AKT survival mechanism. We studied several natural (emodin, rhein, and aloin) and synthetic (AQ2S) anthraquinones, to screen for post- treatment therapeutic benefit in two models of neuronal death, namely hydrogen peroxide (H2O2) and staurosporine (STS)-induced injury. Treatment with emodin, rhein, or aloin failed to reduce H2O2 injury. Moreover, consistent with emodin behaving like a mild toxin, it exacerbated oxidative injury at the highest concentration used (50 mu M) in our post-treatment paradigm, and potently inhibited AKT. In contrast, AQ2S was neuroprotective. It reduced H2O2 injury at 50 and 75 mu M. In addition, AQ2S potently inhibited staurosporine (STS)-induced injury. The mechanisms of action involve caspase inhibition and AKT activation. However, blockade of AKT signaling with LY294002 failed to abolish AQ2S-mediated protection on the STS assay. This is the first study to report that AQ2S is a new neuroprotective compound and a novel caspase inhibitor. Cell Death and Disease (2013) 4, e451; doi:10.1038/cddis.2012.187; published online 10 January 2013
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