SELECTIVE EXPRESSION OF CYTOCHROME-P450 CYP3A MESSENGER-RNAS IN EMBRYONIC AND ADULT HUMAN LIVER

SELECTIVE EXPRESSION OF CYTOCHROME-P450 CYP3A MESSENGER-RNAS IN EMBRYONIC AND ADULT HUMAN LIVER
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DOI:
10.1097/00008571-199402000-00002
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发表时间:
1994-02-01
期刊:
PHARMACOGENETICS
影响因子:
--
通讯作者:
GUZELIAN, PS
GUZELIAN, PS
中科院分区:
其他
文献类型:
--
作者:
SCHUETZ, JD;BEACH, DL;GUZELIAN, PS

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人CYP 3A P450家族由至少四个高度同源的基因组成,在肝脏中显著表达。为了单独研究CYP 3A家族成员的表达,我们制备了对每种CYP 3A mRNA特异的寡核苷酸,并使用北方印迹分析和/或聚合酶链反应来检查来自成人和胎儿肝脏的RNA,以了解发育过程中CYP 3A形式表达的变化。我们发现,CYP 3A 4(P450 NF)mRNA,出生后只能通过北方印迹法检测到,在成年样本中高度可变(10倍),并且与大鼠对应物(CYP 3A 1/2)不同,不受性别影响。与此相反,CYP 3A 7(HFLa)mRNA,以前被认为是局限于胎儿肝脏的形式,被发现在所有测试样品的胎儿肝脏,以及在7/13成人肝脏(54%)。CYP 3A 5(HLp 2),一种在所有胎儿样本中也发现的mRNA,在这13名成人中的3名(23%)中检测到,这3名成人中的2名共表达CYP 3A 7 mRNA。CYP 3A 5和CYP 3A 7在两种性别的胎儿肝脏中以相似的水平表达。此外,胎儿肝脏中的CYP 3A 7表达似乎变化较小(
The human CYP3A P450 family, composed of at least four highly homologous genes, is expressed prominently in the liver. To investigate the expression of CYP3A family members individually, we prepared oligonucleotides specific for each CYP3A mRNA and used Northern blot analysis and/or polymerase chain reaction to examine RNA from adult and fetal liver for variation in expression of the CYP3A forms during development. We found that CYP3A4 (P450NF) mRNA, was only detectable by Northern blot postnatally, was highly variable (10-fold) among the adult samples, and, unlike its rat counterparts (CYP3A1/2), was not influenced by gender. In contrast, CYP3A7 (HFLa) mRNA, a form previously thought to be confined to fetal liver, was found in all tested samples of fetal liver as well as in seven of 13 adult livers (54%). CYP3A5 (HLp2), an mRNA also found in atl the fetal samples, was detected in three of these 13 adults (23%) and two of these three co-expressed CYP3A7 mRNA. CYP3A5 and CYP3A7 are expressed at similar levels in fetal liver from either gender. Moreover, CYP3A7 expression in fetal liver appears less variable (