Dallman P R
J Clin Invest. 1967 Nov;46(11):1819-27. doi: 10.1172/JCI105672.
The repair of cytochrome oxidase depletion during the treatment of copper deficiency was studied in the rat. The purpose of this study was to distinguish the role of new cell production from the possibly more specific role of mitochondrial turnover in determining the rate of this repair. In rats on a copper-deficient regimen until 2.5-3 months of age, activities of cytochrome oxidase expressed as per cent of control were as follows: skeletal muscle (quadratus lumborum), 18%; heart, 27%; liver, 34%; and intestinal mucosa, 34%. After 2-3 days of dietary supplementation with cupric acetate, repair of decreased cytochrome oxidase activity in intestinal mucosa is complete. Histochemical studies indicated that this repair starts in the newly differentiating cells at the base of the villus and then progresses toward the tip of the villus at a rate approximating the normal rate of migration of the mucosal cells. In liver and skeletal muscle, cytochrome oxidase activity returned to control values after 10-15 days of treatment with cupric acetate. In heart muscle, control values were approached more slowly as indicated both by activity of the enzyme and by mitochondrial difference spectra which reflect enzyme concentration. Although cytochrome oxidase repair in the intestine appeared to be limited by the rate of production of new mucosal cells, the rate of repair in liver and skeletal muscle was several times too rapid to be accounted for by known rates of new cell production. Incorporation of tritiated thymidine into DNA in these tissues in both the deficiency state and during repair indicated no major differences in new cell production compared to that of control animals. However, the time required for cytochrome oxidase repair in liver was similar to the turnover reported for other mitochondrial constituents in this tissue. The rate of cytochrome oxidase repair may therefore be more directly determined by the rate of synthesis of new mitochondrial material than by the rate of production of new cells.
在大鼠中研究了铜缺乏治疗期间细胞色素氧化酶耗竭的修复情况。本研究的目的是区分新细胞产生的作用与线粒体更新在决定这种修复速率方面可能更具特异性的作用。在缺铜方案下饲养至2.5 - 3月龄的大鼠中，以对照百分比表示的细胞色素氧化酶活性如下：骨骼肌（腰方肌），18%；心脏，27%；肝脏，34%；肠黏膜，34%。用醋酸铜进行饮食补充2 - 3天后，肠黏膜中细胞色素氧化酶活性的降低得到完全修复。组织化学研究表明，这种修复始于绒毛底部新分化的细胞，然后以接近黏膜细胞正常迁移速率的速度向绒毛顶端推进。在肝脏和骨骼肌中，用醋酸铜治疗10 - 15天后，细胞色素氧化酶活性恢复到对照值。在心肌中，无论是通过酶活性还是反映酶浓度的线粒体差异光谱都表明，接近对照值的速度较慢。尽管肠道中细胞色素氧化酶的修复似乎受新黏膜细胞产生速率的限制，但肝脏和骨骼肌中的修复速率太快，无法用已知的新细胞产生速率来解释。在缺乏状态和修复过程中，这些组织中氚标记胸腺嘧啶核苷掺入DNA的情况表明，与对照动物相比，新细胞产生没有重大差异。然而，肝脏中细胞色素氧化酶修复所需的时间与该组织中其他线粒体成分报道的更新时间相似。因此，细胞色素氧化酶的修复速率可能更直接地由新线粒体物质的合成速率决定，而不是由新细胞的产生速率决定。
