Regucalcin confers resistance to amyloid-β toxicity in neuronally differentiated PC12 cells.
Regucalcin confers resistance to amyloid-β toxicity in neuronally differentiated PC12 cells.
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DOI：
10.1002/2211-5463.12374
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发表时间：
2018-03
期刊：
影响因子：
2.6
通讯作者：
Kaneda N
中科院分区：
文献类型：
--
作者：
Murata T;Yamaguchi M;Kohno S;Takahashi C;Kakimoto M;Sugimura Y;Kamihara M;Hikita K;Kaneda N
淀粉样蛋白-β（Aβ）是淀粉样斑块的主要成分，与阿尔茨海默病的发病机制广泛相关。钙结合蛋白regucalcin（RGN）通过调节细胞内钙稳态、各种信号通路和基因表达系统在维持细胞功能方面发挥多种作用。在这里，我们研究了RGN对神经分化的PC 12细胞中Aβ诱导的细胞毒性的功能作用。RGN的过表达通过减少线粒体功能障碍和caspase激活来减少Aβ诱导的细胞凋亡。它还减弱了Aβ诱导的活性氧产生和氧化损伤，并减少了Aβ诱导的一氧化氮（NO）过量产生、核因子-κB对诱导型NO合酶的上调以及亚硝化损伤。有趣的是，RGN的遗传破坏增加了神经分化的PC 12细胞对Aβ毒性的易感性。因此，RGN对Aβ诱导的氧化和亚硝化应激具有抗氧化活性，并可能对Aβ诱导的阿尔茨海默病神经毒性发挥保护作用。
Amyloid‐β (Aβ), a primary component of amyloid plaques, has been widely associated with the pathogenesis of Alzheimer's disease. The Ca2+‐binding protein regucalcin (RGN) plays multiple roles in maintaining cell functions by regulating intracellular calcium homeostasis, various signaling pathways, and gene expression systems. Here, we investigated the functional role of RGN against Aβ‐induced cytotoxicity in neuronally differentiated PC12 cells. Overexpression of RGN reduced Aβ‐induced apoptosis by reducing mitochondrial dysfunction and caspase activation. It also attenuated Aβ‐induced reactive oxygen species production and oxidative damage and decreased Aβ‐induced nitric oxide (NO) overproduction, upregulation of inducible NO synthase by nuclear factor‐κB, and nitrosative damage. Interestingly, the genetic disruption of RGN increased the susceptibility of neuronally differentiated PC12 cells to Aβ toxicity. Thus, RGN possesses antioxidant activity against Aβ‐induced oxidative and nitrosative stress and may play protective roles against Aβ‐induced neurotoxicity in Alzheimer's disease.
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