Bisaglia M, Venezia V, Biglieri M, Russo C, Mancini F, Milanese C, Schettini G
Pharmacology and Neuroscience (IST), National Cancer Research Institute (IST), c/o Advanced Biotechnology Center (CBA), L.go R. Benzi 10, 16132, Genova, Italy.
Neurochem Int. 2004 Feb;44(3):161-70. doi: 10.1016/s0197-0186(03)00131-1.
The present work shows that alpha-glycerylphosphorylethanolamine (alpha-GPE) is effective in recovering astrocytes from mitochondrial membrane integrity and potential derangement and cellular oxidative stress that occur under amyloid beta-peptides-induced reactive gliosis.alpha-Glycerylphosphorylethanolamine (alpha-GPE), a new compound with nootropic properties, known to improve in vivo the learning and memory processes, has been tested for its protective properties on an in vitro model of degeneration. Rat primary astrocytic cultures treated with two amyloid-derived peptides, Abeta((1-40)) and Abeta(3(pE)-42), showed a marked reduction of the mitochondrial redox activity and membrane potential, together with an increase of oxidative species production. Plasma membrane lipid peroxidation (LPO) as well as generation of peroxides is greatly increased under Abeta-peptides toxicity. These features, typical of the reactive gliosis that accompanies neuronal degeneration, were readily recovered by pretreatment with alpha-GPE. alpha-GPE, likely improving the fluidity of cell membrane, has the potential to recover astrocytes from the general redox derangement induced by different amyloid fragments and possibly to protect from inflammation, gliosis and neurodegeneration. This is the first evidence of an antioxidant effect of the ethanolamine derivative on a rat model of chronic gliosis.
目前的研究表明,α-甘油磷酰乙醇胺(α-GPE)可有效恢复淀粉样β肽诱导的反应性胶质增生过程中出现的星形胶质细胞线粒体膜完整性、电位紊乱及细胞氧化应激。α-甘油磷酰乙醇胺(α-GPE)是一种具有促智特性的新化合物,已知其可在体内改善学习和记忆过程,已针对其在体外变性模型中的保护特性进行了测试。用两种淀粉样衍生肽Abeta((1-40))和Abeta(3(pE)-42)处理的大鼠原代星形胶质细胞培养物显示线粒体氧化还原活性和膜电位显著降低,同时氧化物质生成增加。在Abeta肽毒性作用下,质膜脂质过氧化(LPO)以及过氧化物的生成大幅增加。这些伴随神经元变性的反应性胶质增生的典型特征,通过用α-GPE预处理可迅速恢复。α-GPE可能改善细胞膜的流动性,有潜力从不同淀粉样片段诱导的一般氧化还原紊乱中恢复星形胶质细胞,并可能预防炎症、胶质增生和神经变性。这是乙醇胺衍生物对大鼠慢性胶质增生模型具有抗氧化作用的首个证据。