CYP2C8 and CYP2C9 mRNA expression profile in the human fetus.
CYP2C8 and CYP2C9 mRNA expression profile in the human fetus.
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DOI：
10.3389/fgene.2014.00058
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发表时间：
2014
影响因子：
3.7
通讯作者：
Ekström L
中科院分区：
文献类型：
--
作者：
Johansson M;Strahm E;Rane A;Ekström L
CYP2C8和CYP2C9参与了包括布洛芬在内的几种非甾体抗炎药的失活。CYP2C9是人肝脏中的主要形式，而CYP2C8已被认为是胎儿肝脏中的主要CYP2C酶。妊娠早期CYP2C9蛋白表达较低，仅为成人水平的1%左右，而胎儿期CYP2C8/9 mRNA水平尚未测定。本研究检测了20例成人和60例胎儿肝脏组织标本中CYP2C8和CYP2C9的mRNA表达水平。在胎儿肾脏（n = 43）、肾上腺（n = 46）和肺（n = 37）中也测定了表达谱。此外，还测定了胎儿和成人肝微粒体抗布洛芬羟基化的活性。成人肝脏样本CYP2C8和CYP2C9 mRNA的表达水平分别是胎儿肝脏样本的140倍和400倍。与此相一致的是，布洛芬在成人肝微粒体中的羟基化程度高出40倍。胎儿肝脏CYP2C8 mRNA的丰度是CYP2C9 mRNA的3倍。此外，CYP2C8在所有被调查的胎儿组织中一致表达，而CYP2C9基因表达仅限于胎儿的肝脏。我们的结果表明，在妊娠早期，CYP2C8比CYP2C9发挥更重要的生理作用。
CYP2C8 and CYP2C9 are involved in the inactivation of several non-steroidal anti-inflammatory drugs, including ibuprofen. CYP2C9 is the major form in human liver whereas CYP2C8 has been proposed to be the main CYP2C enzyme in fetal liver. The protein expression of CYP2C9 in the first trimester is low, only about 1% of the adult values, whereas the mRNA levels of CYP2C8/9 have not been determined at the fetal stage. In this study the mRNA expression levels of CYP2C8 and CYP2C9 were determined in 20 adult and 60 fetal liver tissue specimens. The expression profiles in fetal kidneys (n = 43), adrenals (n = 46), and lungs (n = 37) were also determined. Moreover the activity against ibuprofen hydroxylation was determined in fetus and adult liver microsomes. Adult liver samples expressed 140 and 400 times higher levels of CYP2C8 and CYP2C9 mRNA, respectively, as compared to fetal liver samples. Consistent with this, the hydroxylation of ibuprofen was 40 times higher in the adult liver microsomes. Hepatic CYP2C8 mRNA was three times more abundant than CYP2C9 mRNA in the fetus. Moreover, CYP2C8 were consistently expressed in all fetal tissues investigated, whereas CYP2C9 gene expression was confined to the liver in fetuses. Our results indicate that CYP2C8 plays a more important physiological role than CYP2C9 in the first trimester.