The Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA.
J Mol Neurosci. 2009 Sep;39(1-2):157-68. doi: 10.1007/s12031-008-9170-7. Epub 2009 Jan 15.
Resveratrol, a naturally occurring polyphenol, exhibits antioxidant, antiaging, and anticancer activity. Resveratrol has also been shown to inhibit tumor initiation, promotion, and progression in a variety of cell culture systems. Earlier, we showed that paraquat, a bipyridyl herbicide, triggers endoplasmic reticulum stress, cell dysfunction, and dopaminergic cell death. Due to its antioxidant activity, we assessed the ability of resveratrol to rescue cells from the toxic effects of paraquat. While resveratrol did not have any protective effect at low concentrations, it triggered endoplasmic reticulum (ER) stress-induced cell death at higher concentrations (50-250 microM). The present study was carried out to determine the mechanism by which resveratrol triggers ER stress and cell death in dopaminergic N27 cells. Our studies demonstrate that resveratrol triggers ER stress and cell dysfunction, caspase activation, p23 cleavage and inhibition of proteasomal activity in dopaminergic N27 cells. While over expression of uncleavable p23 was associated with decreased cell death, downregulation of p23 protein expression by siRNA resulted in enhancement of ER stress-induced cell death triggered by resveratrol indicating a protective role for the small co-chaperone p23 in dopaminergic cell death.
白藜芦醇是一种天然存在的多酚，具有抗氧化、抗衰老和抗癌活性。白藜芦醇还被证明可以抑制多种细胞培养系统中的肿瘤起始、促进和进展。早些时候，我们表明百草枯，一种双吡啶除草剂，引发内质网应激、细胞功能障碍和多巴胺能细胞死亡。由于其抗氧化活性，我们评估了白藜芦醇从百草枯的毒性作用中拯救细胞的能力。虽然白藜芦醇在低浓度时没有任何保护作用，但它在较高浓度（50-250 μM）时引发内质网（ER）应激诱导的细胞死亡。本研究旨在确定白藜芦醇在多巴胺能 N27 细胞中引发 ER 应激和细胞死亡的机制。我们的研究表明，白藜芦醇在多巴胺能 N27 细胞中引发 ER 应激和细胞功能障碍、半胱天冬酶激活、p23 切割和蛋白酶体活性抑制。虽然不可切割的 p23 的过表达与细胞死亡减少有关，但 siRNA 下调 p23 蛋白表达导致白藜芦醇引发的 ER 应激诱导的细胞死亡增强，表明小伴侣蛋白 p23 在多巴胺能细胞死亡中具有保护作用。
