Yamauchi A, Imai E, Noguchi T, Tanaka T, Yamamoto S, Mikami H, Fukuhara Y, Fujii M, Orita Y, Kamada T
First Department of Medicine, Osaka University Medical School, Japan.
Metabolism. 1989 May;38(5):421-4. doi: 10.1016/0026-0495(89)90191-1.
The effects of chronic renal failure on the level of albumin mRNA and the transcription rate of the albumin gene were studied in seven of eight nephrectomized rats. A paired feeding procedure was employed to eliminate a nutritional difference between sham-operated control and uremic rats. Total RNA was isolated from the livers of control and uremic rats fasted for 24 or 48 hours. The mRNA level was measured by RNA-cDNA dot blot hybridization, and the transcription rate was measured by the "run-on" transcription assay in isolated nuclei. The albumin mRNA levels in uremic rat livers were reduced to 75% at the 24-hour fasted state, and to 45% at 48-hour fasted state compared with those in the respective control groups. There was no difference in the level of beta-actin mRNA between these groups. However, there was no difference in the transcription rate of the albumin gene between control and uremic rats. Northern analysis showed that albumin mRNA isolated from uremic rat liver was identical in size with that from the control. These results suggested that a posttranscriptional process, involving the destabilization of cytoplasmic mRNA, is responsible for the uremia-induced repression of albumin synthesis.
在八只肾切除大鼠中的七只身上研究了慢性肾功能衰竭对白蛋白mRNA水平及白蛋白基因转录率的影响。采用配对喂养程序以消除假手术对照组和尿毒症大鼠之间的营养差异。从禁食24或48小时的对照大鼠和尿毒症大鼠的肝脏中分离总RNA。通过RNA-cDNA斑点印迹杂交法测量mRNA水平，通过分离细胞核中的“连续”转录分析法测量转录率。与各自对照组相比，尿毒症大鼠肝脏中的白蛋白mRNA水平在禁食24小时状态下降至75%，在禁食48小时状态下降至45%。这些组之间β-肌动蛋白mRNA水平没有差异。然而，对照大鼠和尿毒症大鼠之间白蛋白基因的转录率没有差异。Northern分析表明，从尿毒症大鼠肝脏分离的白蛋白mRNA在大小上与对照大鼠的相同。这些结果提示，一个涉及细胞质mRNA去稳定化的转录后过程，是尿毒症诱导的白蛋白合成抑制的原因。
