Bièche Ivan, Narjoz Cèline, Asselah Tarik, Vacher Sophie, Marcellin Patrick, Lidereau Rosette, Beaune Philippe, de Waziers Isabelle
INSERM, UMR735, St-Cloud, F-92210 Centre Renè Huguenin, FNCLCC, St-Cloud, F-92211, France.
Pharmacogenet Genomics. 2007 Sep;17(9):731-42. doi: 10.1097/FPC.0b013e32810f2e58.
The aim of this work was to study simultaneously the expression profile of the 23 CYP mRNAs of CYP1, CTP2 and CYP3 families in 22 different human tissues namely adrenal gland, bladder, bone marrow, colon, fetal liver, heart, kidney, liver, lung, mammary gland, ovary, placenta, prostate, salivary gland, skeletal muscle, small intestine, spleen, testis, thymus, thyroid, trachea and uterus.
Analysis of the mRNA levels of each of these CYP isoforms was performed on total RNA from pooled specimens of human organs using reverse transcriptase-PCR-based CYP mRNA assays previously validated for their sensitivity and their specificity.
Our results confirmed previously reported data in the literature concerning isoforms expression in the most currently studied tissues. Moreover, they provided a great deal of new information, mainly about the expression of mRNA of little-known CYP isoforms. Among the 23 CYP isoforms studied, 12 were mainly hepatic (CYP1A2, 2A6, 2A7, 2A13, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4 and 3A43). Two CYP mRNAs were predominantly expressed in several extrahepatic tissues: CYP1B1 mRNA was the predominant CYP in seven extrahepatic tissues (bone marrow, kidney, mammary gland, prostate, spleen, thyroid and uterus) and CYP2J2 in four extrahepatic tissues (heart, placenta, salivary gland and skeletal muscle). Finally, some CYPs were nearly exclusively expressed in only one extrahepatic tissue. CYP2R1 was found in testis, CYP2U1 in the thymus and CYP2F1 in the respiratory tract (lung and trachea).
This description will broaden the understanding of the physiological functions of these CYPs.
本研究旨在同时研究CYP1、CYP2和CYP3家族的23种CYP mRNA在22种不同人体组织中的表达谱,这些组织包括肾上腺、膀胱、骨髓、结肠、胎儿肝脏、心脏、肾脏、肝脏、肺、乳腺、卵巢、胎盘、前列腺、唾液腺、骨骼肌、小肠、脾脏、睾丸、胸腺、甲状腺、气管和子宫。
使用先前已验证其敏感性和特异性的基于逆转录酶 - PCR的CYP mRNA检测方法,对来自人体器官混合标本的总RNA进行这些CYP同工型各自mRNA水平的分析。
我们的结果证实了文献中先前报道的有关目前研究最多的组织中同工型表达的数据。此外,它们还提供了大量新信息,主要是关于鲜为人知的CYP同工型mRNA的表达。在所研究的23种CYP同工型中,12种主要在肝脏中表达(CYP1A2、2A6、2A7、2A13、2C8、2C9、2C18、2C19、2D6、2E1、3A4和3A43)。两种CYP mRNA在几种肝外组织中主要表达:CYP1B1 mRNA是七种肝外组织(骨髓、肾脏、乳腺、前列腺、脾脏、甲状腺和子宫)中的主要CYP,CYP2J2在四种肝外组织(心脏、胎盘、唾液腺和骨骼肌)中主要表达。最后,一些CYP几乎仅在一种肝外组织中表达。CYP2R1在睾丸中发现,CYP2U1在胸腺中发现,CYP2F1在呼吸道(肺和气管)中发现。
这一描述将拓宽对这些CYP生理功能的理解。