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铝诱导的类阿尔茨海默病状态对大鼠肝脏、脑和心脏线粒体氧化能量代谢的影响。

Effect of aluminium-induced Alzheimer like condition on oxidative energy metabolism in rat liver, brain and heart mitochondria.

作者信息

Swegert C V, Dave K R, Katyare S S

机构信息

Department of Biochemistry, Faculty of Science, MS University of Baroda, India.

出版信息

Mech Ageing Dev. 1999 Dec 7;112(1):27-42. doi: 10.1016/s0047-6374(99)00051-2.

DOI:10.1016/s0047-6374(99)00051-2
PMID:10656181
Abstract

Prolonged exposure of rats to aluminium (Al) can result in an Alzheimer-like condition. To get better insights into the biochemical defects underlying AD, senility and ageing we exposed rats for long durations (90-100 days) to soluble salt of aluminium (AlCl3) and checked its influence on mitochondrial respiratory activity in the liver, brain and heart. In the liver and brain mitochondria the ADP/O ratio was impaired with NAD+ linked substrates. State three respiration decreased with glutamate in the liver. For succinate, the ADP/O ratio decreased in the liver mitochondria while state three and four respiration decreased in the brain mitochondria. In both the tissues respiration rates decreased with ascorbate + TMPD as the substrate. In the heart mitochondria ADP/O ratios with NAD+ linked substrates decreased, while respiration rates increased with all the substrates except for ascorbate + TMPD. Temperature kinetics data showed different effects on ATPase in the mitochondria from the three tissues. Data on lipid/phospholipid profiles suggested that the observed changes in energy metabolism were not mediated via lipid changes. Long-term exposure to Al resulted in approximately 100% increase in Al content of liver and brain mitochondria but in the heart there was phenomenal 11-fold increase, indicating thereby that the effects of Al exposure were indirect rather than direct due to Al accumulation.

摘要

大鼠长期接触铝(Al)会导致类似阿尔茨海默病的状况。为了更深入了解阿尔茨海默病、衰老和老化背后的生化缺陷,我们将大鼠长时间(90 - 100天)暴露于铝的可溶性盐(AlCl3)中,并检查其对肝脏、大脑和心脏线粒体呼吸活性的影响。在肝脏和大脑线粒体中,与NAD + 相关底物的ADP/O比值受损。在肝脏中,以谷氨酸为底物时,状态3呼吸降低。对于琥珀酸,肝脏线粒体中的ADP/O比值降低,而大脑线粒体中的状态3和状态4呼吸降低。在这两种组织中,以抗坏血酸 + TMPD为底物时呼吸速率降低。在心脏线粒体中,与NAD + 相关底物的ADP/O比值降低,而除抗坏血酸 + TMPD外,所有底物的呼吸速率均增加。温度动力学数据显示对三种组织线粒体中的ATP酶有不同影响。脂质/磷脂谱数据表明,观察到的能量代谢变化不是通过脂质变化介导的。长期接触铝导致肝脏和大脑线粒体中的铝含量增加约100%,但在心脏中铝含量显著增加了11倍,从而表明铝暴露的影响是间接的,而非由于铝积累导致的直接影响。

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