Jang Jung-Hee, Surh Young-Joon
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Free Radic Biol Med. 2003 Apr 15;34(8):1100-10. doi: 10.1016/s0891-5849(03)00062-5.
Beta-amyloid peptide is considered to be responsible for the formation of senile plaques that accumulate in the brains of patients with Alzheimer's disease. There has been compelling evidence supporting the idea that beta-amyloid-induced cytotoxicity is mediated through the generation of reactive oxygen intermediates (ROIs). Considerable attention has been focused on identifying phytochemicals that are able to scavenge excess ROIs, thereby protecting against oxidative stress and cell death. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a phytoalexin found in the skin of grapes, has strong antioxidative properties that have been associated with the protective effects of red wine consumption against coronary heart disease ("the French paradox"). In this study, we have investigated the effects of resveratrol on beta-amyloid-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with beta-amyloid exhibited increased accumulation of intracellular ROI and underwent apoptotic death as determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL staining). Beta-amyloid treatment also led to the decreased mitochondrial membrane potential, the cleavage of poly(ADP-ribose)polymerase, an increase in the Bax/Bcl-X(L) ratio, and activation of c-Jun N-terminal kinase. Resveratrol attenuated beta-amyloid-induced cytotoxicity, apoptotic features, and intracellular ROI accumulation. Beta-amyloid transiently induced activation of NF-kappaB in PC12 cells, which was suppressed by resveratrol pretreatment.
β-淀粉样肽被认为是导致老年斑形成的原因，这些老年斑会在阿尔茨海默病患者的大脑中积聚。有确凿的证据支持这样的观点，即β-淀粉样蛋白诱导的细胞毒性是通过活性氧中间体（ROIs）的产生介导的。相当多的注意力集中在鉴定能够清除过量ROIs的植物化学物质上，从而预防氧化应激和细胞死亡。白藜芦醇（3,5,4'-三羟基反式芪）是一种在葡萄皮中发现的植物抗毒素，具有很强的抗氧化特性，这与饮用红酒对冠心病的保护作用（“法国悖论”）有关。在这项研究中，我们研究了白藜芦醇对培养的大鼠嗜铬细胞瘤（PC12）细胞中β-淀粉样蛋白诱导的氧化细胞死亡的影响。用β-淀粉样蛋白处理的PC12细胞表现出细胞内ROI积累增加，并通过特征性形态学改变和原位末端标记阳性（TUNEL染色）确定发生凋亡死亡。β-淀粉样蛋白处理还导致线粒体膜电位降低、聚（ADP-核糖）聚合酶的裂解、Bax/Bcl-X(L)比值增加以及c-Jun N末端激酶的激活。白藜芦醇减弱了β-淀粉样蛋白诱导的细胞毒性、凋亡特征和细胞内ROI积累。β-淀粉样蛋白短暂诱导PC12细胞中NF-κB的激活，而白藜芦醇预处理可抑制这种激活。
