期刊
EXPERIMENTAL GERONTOLOGY
卷 46, 期 1, 页码 30-37出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2010.09.013
关键词
Puerarin; Reactive oxygen species; Apoptosis; Sporadic Alzheimer's disease; Cybrids
资金
- Hainan Science and Technology key project [090126]
Mitochondrial oxidative stress induced by reactive oxygen species (ROS) has been strongly associated with the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD). We used mitochondrial transgenic neuronal cell cybrid models of sporadic AD (SAD), which overproduce ROS compared to control cybrids, to investigate the protective effects of puerarin, an isoflavone purified from Chinese herb radix of Pueraria lobata, on viability, endogenous ROS and intracellular signaling pathways. SAD cybrids had increased apoptosis and increased accumulation of ROS that was inhibited by puerarin. Western blotting demonstrated that SAD cybrids had increased basal activation of the caspase-3, p38 and c-Jun N-terminal kinase (INK) that were inhibited by puerarin. Puerarin was also found to decrease Bax/Bcl-2 ratio. These results suggest that expression of SAD mitochondrial genes in cybrids activates oxidative-stress-related signaling pathways and reduces viability, and that the protective effects of puerarin inhibit oxidative-stress-induced apoptosis through down-regulation of Bax/Bcl-2 ratio, which blocks the activation of JNK, p38 and caspase-3. Therefore, puerarin may act as an intracellular ROS scavenger, and protect neurons against oxidative-stress-induced apoptosis. 2010 Elsevier Inc. All rights reserved.
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