Djouadi F, Bastin J, Gilbert T, Rötig A, Rustin P, Merlet-Benichou C
Institut National de la Santé et de la Recherche Médicale Unité 319 Université Paris, France.
Am J Physiol. 1994 Jul;267(1 Pt 1):C245-54. doi: 10.1152/ajpcell.1994.267.1.C245.
We have previously shown that the activity of several mitochondrial oxidative enzymes increased greatly in the medullary thick ascending limb of Henle's loop (MTAL) of developing rat kidney between 16 days after birth and the adult stage. These changes were triggered by the postnatal rise in circulating glucocorticoids. To determine whether these increases are related to a mitochondrial biogenesis we have studied the changes in mitochondrial density of MTAL cells and mitochondrial DNA content in the inner stripe of the outer medulla during the postnatal period. The activities of respiratory chain (RC) complexes II and IV, located in the inner mitochondrial membrane (IMM), were also assayed, and developmental changes in the ultrastructure of the IMM were quantified. Quantitative electron-microscopic data showed a doubling in mitochondrial density from day 16 to the adult, accompanied by twofold increase in mitochondrial DNA, as determined by slot-blot experiments. The surface density of IMM increased by 77%, and there was a concomitant large rise in the activity of both RC enzymes. A possible role of glucocorticoids on the regulation of mitochondrial biogenesis was examined in similar experiments performed in adrenalectomized rat pups. The data demonstrated that glucocorticoids are essential for the rise in RC enzymes and the development of IMM but do not regulate postnatal changes in mitochondrial density and mitochondrial DNA content. Finally, ontogenic changes in oxidative capacities of MTAL cells could be a critical factor in the development of kidney urine concentrating mechanisms in weanling rats.
我们先前已经表明，在出生后16天到成年阶段之间，发育中大鼠肾脏的髓袢升支粗段（MTAL）中几种线粒体氧化酶的活性大幅增加。这些变化是由出生后循环糖皮质激素的升高引发的。为了确定这些增加是否与线粒体生物发生有关，我们研究了出生后时期外髓质内带MTAL细胞的线粒体密度和线粒体DNA含量的变化。还测定了位于线粒体内膜（IMM）的呼吸链（RC）复合物II和IV的活性，并对IMM超微结构的发育变化进行了量化。定量电子显微镜数据显示，从第16天到成年，线粒体密度增加了一倍，同时通过狭缝印迹实验确定线粒体DNA增加了两倍。IMM的表面密度增加了77%，并且两种RC酶的活性同时大幅上升。在对肾上腺切除的幼鼠进行的类似实验中，研究了糖皮质激素对线粒体生物发生调节的可能作用。数据表明，糖皮质激素对于RC酶的升高和IMM的发育至关重要，但不调节出生后线粒体密度和线粒体DNA含量的变化。最后，MTAL细胞氧化能力的个体发育变化可能是断奶大鼠肾脏尿液浓缩机制发育的关键因素。
