Studies on the Mechanism of Cell Deterioration for the Prevention of Aging through Dietary Life

传统上，脂质过氧化被认为是氧自由基对大脑造成损害的主要过程，随后会导致某些形式的与年龄相关的恶化。大脑具有高耗氧量和丰富的多不饱和脂肪酸，因此面临氧化损伤的风险。尽管有大量的报道表明脂质过氧化与神经退行性疾病有关，但脂质过氧化的确切靶点仍不清楚。本研究的目的是阐明神经细胞中脂质过氧化氢的确切靶点。在这项研究中，我们展示了磷脂酰胆碱(PCOOH)在分化为神经细胞前后对PC12细胞的有害影响。与以类似方式处理的未分化细胞相比，经PCOOH处理的分化细胞的细胞存活率显著降低。PCOOH破坏了主要由微管蛋白组成的神经突起和神经元微管的形成。我们的结果表明，分化的细胞比未分化的细胞更容易受到PCOOH的攻击，并且PCOOH可以攻击微管-微管系统。这是首次阐明神经退行性疾病早期产生的PCOOH对神经细胞的影响，并阐明脂质氢过氧化的靶点。

Lipid peroxidation traditionally has been regarded as the major process causing damage to the brain by oxygen radicals and, subsequently, some forms of age-related deterioration. The brain, with its high oxygen consumption and abundance of polyunsaturated fatty acids, is at risk for oxidative damage. Although a great number of reports have associated lipid peroxidation with neurodegenerative diseases, the precise target of lipid peroxidation remains unclear. The aim of this study was to clarify the precise target of lipid hydroperoxides in neuronal cells. In this study, we showed the deleterious effect of phosphatidylcholine hydroperoxides (PCOOH) on PC 12 cells before and after differentiation into neuronal cells. Cell viability was significantly decreased in differentiated cells treated with PCOOH compared to undifferentiated cells treated in a similar way. PCOOH disrupted the formation of neurites and neuronal microtubules, which consist mainly of tubulin. Our results showed that differentiated cells were more vulnerable than undifferentiated cells to PCOOH and that PCOOH could attack microtubule-tubulin systems. This is the first study to clarify the effect on neuronal cells of PCOOH produced in the early stage of neurodegenerative disease and to elucidate the target of lipid hydroperoxide.