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肝脏线粒体结构与功能的研究:砷酸盐对体内干扰的形态学和生物化学评估

Studies of hepatic mitochondrial structure and function: morphometric and biochemical evaluation of in vivo perturbation by arsenate.

作者信息

Fowler B A, Woods J S, Schiller C M

出版信息

Lab Invest. 1979 Oct;41(4):313-20.

PMID:491544
Abstract

Ultrastructural morphometric and biochemical studies were conducted on hepatic mitochondria from control rats and rats treated in vivo with arsenate to examine changes in interrelationships between mitochondrial structure and biochemical functions. Morphometric analysis disclosed an over-all 1.2-fold increase in the relative mitochondrial volume density and 1.4-fold increase in the surface density of the inner mitochondrial membrane of arsenate-exposed rats. These structural changes were associated with a 1.5-fold increase in 14C-leucine incorporation into all mitochondrial proteins, which was primarily associated with the acid-insoluble membranous fraction. Mitochondria from arsenate-treated rats showed a marked disruption of normal conformational behavior with depression of nicotinamide adenine dinucleotide (NAD)-linked substrate oxidation and a resulting in vivo increase in the mitochondrial [NAD] to [NADH] ratio. Observed changes in mitochondrial membranes from arsenate exposure also resulted in 1.5- to 2-fold increases in the specific activities of the membrane marker enzymes monoamine oxidase, cytochrome oxidase, and Mg2+-ATPase. Activity of malate dehydrogenase, which is localized in the mitochondrial matrix, was unchanged. The results of this study demonstrate a positive quantitative in vivo correlation between mitochondrial structure and function and indicate a marked dependency upon membrane integrity for normal maintenance of the specific biologic activities performed by this organelle in vivo.

摘要

对对照大鼠和经体内砷酸盐处理的大鼠的肝脏线粒体进行了超微结构形态计量学和生化研究,以检查线粒体结构与生化功能之间相互关系的变化。形态计量学分析显示,砷酸盐暴露大鼠的线粒体相对体积密度总体增加了1.2倍,线粒体内膜表面密度增加了1.4倍。这些结构变化与所有线粒体蛋白质中14C-亮氨酸掺入量增加1.5倍有关,这主要与酸不溶性膜部分有关。砷酸盐处理大鼠的线粒体显示正常构象行为明显破坏,烟酰胺腺嘌呤二核苷酸(NAD)相关底物氧化受到抑制,导致体内线粒体[NAD]与[NADH]比值增加。砷酸盐暴露导致的线粒体膜变化还使膜标记酶单胺氧化酶、细胞色素氧化酶和Mg2+-ATP酶的比活性增加了1.5至2倍。定位于线粒体基质的苹果酸脱氢酶活性未发生变化。本研究结果表明,线粒体结构与功能在体内存在正定量相关性,并表明该细胞器在体内进行的特定生物学活性的正常维持明显依赖于膜的完整性。

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