Van Itallie C M, Van Why S, Thulin G, Kashgarian M, Siegel N J
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Am J Physiol. 1993 Sep;265(3 Pt 1):C712-9. doi: 10.1152/ajpcell.1993.265.3.C712.
Ischemia and reperfusion damage mitochondrial structure and impair respiratory function. In this study, 45 min of renal ischemia followed by varying periods of reflow profoundly depressed the activity of several respiratory complexes in mitochondria isolated from rat kidneys. The respiratory complexes are composed of subunits encoded by both the nuclear and mitochondrial genomes. To determine the role of mitochondrial gene expression in recovery of respiratory function, expression of mitochondrial RNA was examined during reperfusion. Both mature and incompletely processed cytochrome b mRNA levels were depressed after 45 min of ischemia and 15 min of reflow; levels rebounded to above normal after 2 h of reflow and then declined over the next 22 h. Another mitochondrial RNA showed a similar pattern; in contrast, the levels of a nuclear-encoded subunit mRNA for a respiratory enzyme and of 28S rRNA were unchanged. These data demonstrate that renal ischemia followed by reperfusion alters mitochondrial RNA expression. We speculate that mitochondrial RNA turnover is increased in response to continuing injury and that recovery is accompanied by enhanced RNA synthesis.
缺血和再灌注会破坏线粒体结构并损害呼吸功能。在本研究中,大鼠肾脏缺血45分钟后再进行不同时长的复流,会显著降低从大鼠肾脏分离出的线粒体中几种呼吸复合体的活性。呼吸复合体由核基因组和线粒体基因组编码的亚基组成。为了确定线粒体基因表达在呼吸功能恢复中的作用,我们在再灌注过程中检测了线粒体RNA的表达。缺血45分钟和复流15分钟后,成熟和未完全加工的细胞色素b mRNA水平均降低;复流2小时后水平反弹至正常以上,然后在接下来的22小时内下降。另一种线粒体RNA也呈现类似模式;相比之下,一种呼吸酶的核编码亚基mRNA水平和28S rRNA水平未发生变化。这些数据表明,肾脏缺血后再灌注会改变线粒体RNA表达。我们推测,线粒体RNA周转因持续损伤而增加,而恢复伴随着RNA合成增强。