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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Reduced (3H)IP3 binding but unchanged IP3 receptor levels in the rat hippocampus CA1 region following transient global ischemia and tolerance induction.
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Reduced (3H)IP3 binding but unchanged IP3 receptor levels in the rat hippocampus CA1 region following transient global ischemia and tolerance induction.

机译:短暂性整体缺血和耐受诱导后,大鼠海马CA1区的(3H)IP3结合降低,但IP3受体水平未改变。

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摘要

Changes in inositol (1,4,5)-trisphosphate (IP3) binding properties and the protein level of the IP3 receptor have been reported in different pathological conditions in the brain, e.g. cerebral ischemia, Alzheimer's disease, and Huntingtons disease. We used the 4-vessel occlusion model in rat brain to investigate the effect of transient ischemia insults on the IP3 receptor mRNA level, the IP3 receptor protein level and [3H]IP3 binding. Recirculation periods were limited (1-72 h) to avoid the development of delayed neuronal death. We found that the IP3 receptor mRNA levels were decreased after damage-inducing ischemia (9 min) in the hippocampus CA1 and CA3 regions. The mRNA levels were unaltered after tolerance-inducing ischemia (3 min). However, [3H]IP3 binding was significantly reduced after both damage- and tolerance-inducing ischemia in the hippocampus CA1 region. Furthermore, all investigated brain areas showed a decreased [3H]IP3 binding when tolerance-inducing ischemia was followed by a second ischemic insult (3 + 8.5 min ischemia). The IP3 receptor protein levels remained constant in all investigated brain areas. These results indicate that a reduced [3H]IP3 binding capability in the particularly vulnerable areas occurs as an early consequence of cerebral ischemia, before IP3 receptor protein levels are reduced in these areas. Structural or conformational changes altering IP3 binding may be of necessity on the pathway leading to down-regulation of IP3 receptor protein levels, as observed by others.
机译:已经报道了在脑部的不同病理状况下,例如,肌醇(1,4,5)-三磷酸(IP3)结合特性和IP3受体的蛋白质水平的变化。脑缺血,阿尔茨海默氏病和亨廷顿病。我们使用大鼠大脑中的4血管闭塞模型研究短暂性缺血损伤对IP3受体mRNA水平,IP3受体蛋白水平和[3H] IP3结合的影响。循环时间有限(1-72小时),以免发生延迟性神经元死亡。我们发现,在海马CA1和CA3区引起损伤的局部缺血(9分钟)后,IP3受体mRNA水平降低。诱导耐受性缺血(3分钟)后,mRNA水平未改变。但是,在损伤和耐受诱导的海马CA1区缺血后,[3H] IP3结合显着降低。此外,当耐受性诱导的局部缺血继之以第二次局部缺血(3 + 8.5分钟局部缺血)后,所有研究的大脑区域均显示[3H] IP3结合减少。在所有研究的大脑区域中,IP3受体蛋白水平保持恒定。这些结果表明,在脑部局部缺血的早期后果中,特别易受伤害的区域中[3H] IP3的结合能力降低,然后这些区域的IP3受体蛋白水平降低。正如其他人所观察到的那样,改变IP3结合的结构或构象变化可能是导致IP3受体蛋白水平下调的途径。

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