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High cholesterol diet down regulates the activity of activator protein-1 but not nuclear factor-kappa B in rabbit brain.

机译:高胆固醇饮食降低了兔脑中激活蛋白1的活性,但没有调节核因子-κB的活性。

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摘要

Cardiovascular risk factors and alterations in cholesterol metabolism are implicated in the pathogenesis of Alzheimer's dementia (AD). The hypercholesterolemic rabbit model of atheroslerosis and AD was utilized in this study to examine oxidative stress related changes in the brain. The high cholesterol diet induced dramatic increases in plasma and liver cholesterol concentrations, but brain cholesterol levels remained constant. Similar effects have been found regarding lipid oxidation products. The amounts of conjugated dienes, trienes and thiobarbituric acid reactive substances (TBARS) significantly increased in the plasma of cholesterol treated animals while the brain cortex showed no signs of increased lipid peroxidation. The oxidative damage sensitive nuclear transcription factor kappa B (NF-kappaB) and activator protein-1 (AP-1) diverged in their responses. Accordingly, the AP-1 DNA binding activity decreased by more than 50% in brain nuclear protein extracts while the NF-kappaB binding activity remained unaltered by the hypercholesterol diet. These results indicate that despite the relative resistance of the central nervous system to dietary manipulation of its lipid composition and lipid peroxidation products, chronic dietary intake of cholesterol can alter the function of certain proteins involved in regulation of gene expression in the brain.
机译:心血管危险因素和胆固醇代谢改变与阿尔茨海默氏痴呆症(AD)的发病机理有关。本研究利用动脉粥样硬化和AD的高胆固醇血症兔模型检查大脑中与氧化应激相关的变化。高胆固醇饮食引起血浆和肝胆固醇浓度急剧增加,但脑胆固醇水平保持恒定。对于脂质氧化产物已经发现了类似的效果。在胆固醇治疗动物的血浆中,共轭二烯,三烯和硫代巴比妥酸反应性物质(TBARS)的含量显着增加,而大脑皮层没有显示脂质过氧化增加的迹象。氧化损伤敏感核转录因子κB(NF-κB)和激活蛋白-1(AP-1)的反应有所不同。因此,脑核蛋白提取物中的AP-1 DNA结合活性降低了50%以上,而高胆固醇饮食却未改变NF-κB结合活性。这些结果表明,尽管中枢神经系统对饮食中脂类成分和脂质过氧化产物的操作有相对的抵抗力,但长期饮食中胆固醇的摄入仍会改变某些调节大脑基因表达的蛋白质的功能。

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