Altered hepatic gene expression of enzymes involved in energy metabolism in the growth-retarded fetal rat
Altered hepatic gene expression of enzymes involved in energy metabolism in the growth-retarded fetal rat
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DOI：
10.1203/00006450-199603000-00003
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发表时间：
1996-03-01
影响因子：
3.6
通讯作者：
Simmons, RA
中科院分区：
文献类型：
--
作者：
Lane, RH;Flozak, AS;Simmons, RA
胎盘功能不全引起的胎儿宫内发育迟缓是妊娠期常见的并发症。结扎孕鼠双侧子宫动脉是一种模拟人类宫内发育迟缓的模型。IUGR大鼠胎儿肝脏能量和氧化还原状态改变，胎肝ATP/ADP比值降低，胞质NAD（+）/NADH比值升高，线粒体NAD（+）/NADH比值降低。能量代谢的这些关键变化导致IUGR。这些变化在分子水平上的影响在很大程度上是未知的。为了解决这些影响，我们比较了肝mRNA的人口IUGR和正常胎儿和新生儿使用mRNA差异显示，聚合酶链反应为基础的方法，在各种条件下的转录差异测定。我们分离并测序了18个cDNA产物，其mRNA水平在IUGR中与正常胎儿和新生儿肝脏相比升高。这些分析表明，NADH-泛醌氧化还原酶亚基4L mRNA（ND-4L）在IUGR胎儿和新生儿的肝脏显着增加。这表明IUGR可能与参与ATP和NADH生成的基因表达改变有关。因此，我们使用半定量逆转录-聚合酶链式反应技术测定了腺嘌呤核苷酸转运子-2（ANT-2）、葡萄糖-6-磷酸脱氢酶（G6 PD）、线粒体苹果酸脱氢酶（MMD）、鸟氨酸转氨甲酰酶（OTC）和磷酸果糖激酶-2（PFK-2）的mRNA水平。在IUGR胎儿中，ND-4L、ANT-2、G6 PD和MMD mRNA水平显著升高; PFK-2 mRNA水平不变，OTC水平降低。在IUGR新生大鼠中，所有6种酶的mRNA水平均升高，表明生长迟缓新生大鼠出生后的代谢状态仍然异常。子宫胎盘功能不全影响生长迟缓动物的即时和长期代谢环境，并迫使特定的调整，包括与肝脏能量产生有关的mRNA编码酶的表达。
Intrauterine growth retardation (IUGR) resulting from placental insufficiency is a common complication of pregnancy. Bilateral uterine artery ligation of the pregnant rat is a model which mimics intrauterine growth retardation in the human. IUGR rat fetuses have altered hepatic energy and redox states, with reduced fetal hepatic ATP/ADP ratio, increased cytosolic NAD(+)/NADH ratio, and decreased mitochondrial NAD(+)/NADH ratio. These critical changes in energy metabolism contribute to IUGR. The effects of these changes at the molecular level are largely unknown. To address these effects we compared hepatic mRNA populations of IUGR and normal fetuses and neonates using mRNA differential display, a polymerase chain reaction-based method for assaying transcriptional differences under various conditions. We isolated and sequenced 18 cDNA products whose mRNA levels were elevated in IUGR compared with normal fetal and neonatal liver. These analyses demonstrated that NADH-ubiquinone oxireductase subunit 4L mRNA (ND-4L) was significantly increased in liver of IUGR fetuses and neonates. This suggested that IUGR may be associated with altered expression of genes involved in the generation of ATP and NADH. Therefore, we measured mRNA levels of adenine-nucleotide translocator-2 (ANT-2), glucose-6-phosphate dehydrogenase (G6PD), mitochondrial malate dehydrogenase (MMD), ornithine transcarbamylase (OTC), and phosphofructokinase-2 (PFK-2) using a semiquantitative reverse transcriptase-polymerase chain reaction-based technique. In the IUGR fetus, ND-4L, ANT-2, G6PD, and MMD mRNA levels were significantly elevated; PFK-2 mRNA levels were unchanged, and OTC levels were decreased. In the IUGR newborn rat, mRNA levels of all 6 enzymes were increased suggesting that the metabolic state of the growth retarded newborn remains abnormal after birth. Uteroplacental insufficiency affects the immediate and long-term metabolic milieu of the growth retarded animal, and forces specific adjustments, including the expression of mRNA encoding enzymes involved with hepatic energy production.