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首页> 外文期刊>Biochemical Pharmacology >Protection of mitochondrial respiration activity by bilobalide.
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Protection of mitochondrial respiration activity by bilobalide.

机译:银杏内酯对线粒体呼吸活性的保护。

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Mitochondria alteration is an early event in ischemia-induced damage, and its prevention improves tissue survival upon reperfusion. Adenine translocase and complex I activities are rapidly affected by ischemia. Ginkgo biloba extract demonstrates anti-ischemic properties attributable to the terpenoid fraction, mainly due to the presence of bilobalide. The mechanism of the protection afforded by bilobalide is not yet known. In this work, the effects of bilobalide on mitochondrial respiration were investigated. Mitochondria isolated from rats treated with bilobalide (2 to 8 mg/kg) showed a dose-dependent increase in the respiratory control ratio, due to a lower oxygen consumption during state 4. Bilobalide also decreased the sensitivity of oxygen consumption to inhibition of complex I by Amytal or to inhibition of complex III by antimycin A or myxothiazol. There was no protection of complexes IV and V. It also increased the activity of complex I but not of adenine translocase. Similar effects were also obtained in vitro when control mitochondria were preincubated for 1 hr with 0.8 microg/mL bilobalide. Treatment of the rats with 8 mg/kg bilobalide also prevented the ischemia-induced decrease in state 3 of the mitochondrial respiration and thus the decrease in RCR. The protective effect of bilobalide on cellular ATP content observed under ischemic conditions can be correlated with the above observations. By protecting complex I and III activities, bilobalide allows mitochondria to maintain their respiratory activity under ischemic conditions as long as some oxygen is present, thus delaying the onset of ischemia-induced damage. This mechanism provides a possible explanation for the anti-ischemic properties of bilobalide and of Ginkgo biloba extract in therapeutic interventions.
机译:线粒体改变是缺血引起的损伤的早期事件,其预防可提高再灌注后的组织存活率。腺嘌呤的转位酶和复杂的I活动受到缺血的迅速影响。银杏叶提取物表现出可归因于萜类成分的抗缺血特性,这主要是由于存在银杏内酯。银杏内酯提供的保护机制尚不清楚。在这项工作中,研究了白果内酯对线粒体呼吸的影响。从银杏内酯(2至8 mg / kg)处理的大鼠中分离出的线粒体显示出在4号状态下较低的氧气消耗,其呼吸控制率呈剂量依赖性增加。Bilobalide还降低了氧气消耗对复合物I抑制的敏感性。可以通过Amytal或通过抗霉素A或mythothiazol抑制复合物III来实现。没有复合物IV和V的保护。它也增加了复合物I的活性,但没有增加腺嘌呤转位酶的活性。将对照线粒体与0.8 microg / mL银杏内酯预孵育1小时后,在体外也获得了类似的效果。用8 mg / kg银杏内酯治疗大鼠也可预防缺血诱导的线粒体呼吸状态3下降,从而防止RCR下降。在缺血条件下观察到的银杏内酯对细胞ATP含量的保护作用可以与上述观察结果相关。通过保护复杂的I和III活性,白果内酯允许线粒体在缺血条件下只要存在一些氧气就可以维持其呼吸活性,从而延迟了缺血性损伤的发作。该机制为治疗干预中白果内酯和银杏叶提取物的抗缺血特性提供了可能的解释。

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