Keller J N, Hanni K B, Markesbery W R
Sanders-Brown Center on Aging, University of Kentucky, Lexington 40536-0230, USA.
J Neurochem. 1999 Jun;72(6):2601-9. doi: 10.1046/j.1471-4159.1999.0722601.x.
Low-density lipoprotein (LDL) exists within the brain and is highly vulnerable to oxidative modifications. Once formed, oxidized LDL (oxLDL) is capable of eliciting cytotoxicity, differentiation, and inflammation in nonneuronal cells. Although oxLDL has been studied primarily for its role in the development of atherosclerosis, recent studies have identified a possible role for it in neurological disorders associated with oxidative stress. In the present study application of oxLDL, but not LDL, resulted in a dose- and time-dependent death of cultured rat embryonic neurons. Studies using pharmacological inhibitors implicate the involvement of calcium, reactive oxygen species, and caspases in oxLDL-induced neuronal death. Coapplication of oxLDL with either amyloid beta-peptide or glutamate, agents that enhance oxidative stress, resulted in increased neuronal death. Taken together, these data demonstrate that oxLDL induces neuronal death and implicate a possible role for oxLDL in conditions associated with increased levels of reactive oxygen species, including Alzheimer's disease.
低密度脂蛋白（LDL）存在于大脑中，极易发生氧化修饰。一旦形成，氧化型低密度脂蛋白（oxLDL）能够在非神经元细胞中引发细胞毒性、分化和炎症。尽管oxLDL主要因其在动脉粥样硬化发展中的作用而被研究，但最近的研究已经确定了它在与氧化应激相关的神经系统疾病中可能发挥的作用。在本研究中，应用oxLDL而非LDL会导致培养的大鼠胚胎神经元出现剂量和时间依赖性死亡。使用药理学抑制剂的研究表明，钙、活性氧和半胱天冬酶参与了oxLDL诱导的神经元死亡。将oxLDL与淀粉样β肽或谷氨酸（增强氧化应激的物质）共同应用，会导致神经元死亡增加。综上所述，这些数据表明oxLDL会诱导神经元死亡，并暗示oxLDL在与活性氧水平升高相关的疾病（包括阿尔茨海默病）中可能发挥作用。
