Mifflin R C, Moller P C, Papaconstantinou J
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Somat Cell Mol Genet. 1988 Nov;14(6):553-66. doi: 10.1007/BF01535310.
Two genetic loci regulate hepatic alpha-fetoprotein (AFP) mRNA levels in adult mice. The raf locus controls basal levels and the Rif locus determines the degree of induction during liver regeneration. We have investigated the function of each locus during L-ethionine-mediated AFP induction using adult female mice with different Rif/raf genotypes. A single intraperitoneal injection of L-ethionine (0.5 mg/g body weight) resulted in significant triglyceride accumulation in hepatic parenchymal cells and increased AFP synthesis 48-96 h following injection. Hepatic AFP mRNA levels in Balb/cJ mice (high basal level/high induction level during regeneration) were 10- to 30-fold higher than Balb/cCRBL or C3H/He mice (low basal level/high induction level) following ethionine injection, indicating that raf-mediated differences persisted throughout the course of acute ethionine poisoning. The magnitude of this induction was similar to that seen during carbon tetrachloride-induced regeneration. In contrast, C57BL/6 mice (low basal level/low induction level during regeneration) contained hepatic AFP mRNA levels similar to Balb/cCRBL and C3H/He mice following ethionine injection. Thus, Rif-dependent differences seen during liver regeneration were not seen during acute ethionine poisoning. This leads us to conclude that (1) hepatic AFP mRNA induction by ethionine may not be mediated by the Rif locus if Rif is a transcriptional inducer, or (2) if Rif is a transcriptional repressor, it is inactivated equally in all strains during acute ethionine poisoning, unlike during liver regeneration. Hepatic albumin mRNA levels were not affected by ethionine treatment in vivo. L-Ethionine elevated AFP mRNA levels in primary mouse hepatocyte cultures; however, ethionine treatment also increased albumin mRNA levels in vitro.
两个基因位点调控成年小鼠肝脏中甲型胎儿蛋白（AFP）的mRNA水平。raf位点控制基础水平，而Rif位点决定肝脏再生过程中的诱导程度。我们使用具有不同Rif/raf基因型的成年雌性小鼠，研究了每个位点在L-乙硫氨酸介导的AFP诱导过程中的功能。单次腹腔注射L-乙硫氨酸（0.5毫克/克体重）导致肝实质细胞中显著的甘油三酯积累，并在注射后48 - 96小时增加AFP合成。乙硫氨酸注射后，Balb/cJ小鼠（再生期间基础水平高/诱导水平高）的肝脏AFP mRNA水平比Balb/cCRBL或C3H/He小鼠（基础水平低/诱导水平高）高10至30倍，表明raf介导的差异在急性乙硫氨酸中毒过程中持续存在。这种诱导的幅度与四氯化碳诱导的再生过程中所见相似。相比之下，C57BL/6小鼠（再生期间基础水平低/诱导水平低）在乙硫氨酸注射后的肝脏AFP mRNA水平与Balb/cCRBL和C3H/He小鼠相似。因此，在急性乙硫氨酸中毒期间未观察到肝脏再生期间所见的Rif依赖性差异。这使我们得出结论：（1）如果Rif是转录诱导剂，乙硫氨酸诱导肝脏AFP mRNA可能不是由Rif位点介导的；或者（2）如果Rif是转录抑制剂，在急性乙硫氨酸中毒期间它在所有品系中均被同等程度地失活，这与肝脏再生期间不同。体内乙硫氨酸处理不影响肝脏白蛋白mRNA水平。L-乙硫氨酸可提高原代小鼠肝细胞培养物中的AFP mRNA水平；然而，乙硫氨酸处理在体外也会增加白蛋白mRNA水平。
