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Expression pro filing of drug metabolizing enzymes in human myeloblastic and lymphoid cell lines

人成髓细胞和淋巴细胞系中药物代谢酶的表达谱

基本信息

批准号：
12672174
负责人：
TAMURA Hiro-omi
金额：
$ 1.02万
依托单位：
Kyoritsu College of Pharmacy
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

To explore the physiological roles of drug-metabolizing enzymes in peripheral blood cells, we examined which isoforms of cytochrome P450 (CYP) and conjugation enzymes (sulfotransferases (SULTs), UDP-glucuronyl transferases (UGT) and glutathione S-transferases (GST)) families were expressed in human myeloid leukemia cell lines (U937, HL-60 and K562) and lymphoid cell lines (BALL-1, MOLT-4 and Jurkat) by RT-PCR. We observed relatively high expression of CYP1A1, CYP1B1, CYP2A6, CYP2A7, CYP2D6, and CYP2E1 in all cell types, but CYP2A13 and CYP2C9 expression was not detected. Expressions of aryl hydrocarbon (Ah) receptor and Ah receptor nuclear translocater (ARNT), which mediate induction of the CYP1 family, were also detected in all cell types. Cell-type specific expression of CYP3A4 and CYP3A5 was observed in MOLT-4 and K562 cells. Weak, but significant, expression of CYP3A7 was detected in K562 cells. We detected expression of SULT1A1, 1A3 and 1C2 in all cell lines although cell-type specific expressions were observed for SULT1B1 (U937 and Jurkat) and SULT2A1 (K562). Expression of UGT1A family, which is known to metabolize many drugs and xenobiotics, was exclusively observed in MOLT-4 and BALL-1. BALL-1 expressed 8 sub families of UGT1A and MOLT-4 expressed 2 UGT1A sub families. All cell lines expressed GSTA4, P1 and T1, however, GSTM1 expression, which is supposed to detoxify carcinogens in cigarette smoke, was detected only in MOLT-4 cells. Oxidative stress (hydroperoxide) induced CYP3A4 and GSTP1 expressions in K562 cells. Chemical inducers (p-naphthoflavone and 3-methylcholanthren) induced CYP1A1 expression in MOLT-4 cells. The profile of drug-metablizing enzymes in the culture cells reported here provides information that furthers our understanding of the physiological roles of drug metabolizing enzymes in human blood cells.

为了探讨药物代谢酶在外周血中的生理作用，我们采用RT-PCR方法检测了细胞色素P450 （CYP）和偶联酶（硫代转移酶（SULTs）、udp -葡萄糖醛基转移酶（UGT）和谷胱甘肽s -转移酶（GST））家族在人髓性白血病细胞株（U937、HL-60和K562）和淋巴样细胞株（BALL-1、MOLT-4和Jurkat）中的表达。我们观察到CYP1A1、CYP1B1、CYP2A6、CYP2A7、CYP2D6和CYP2E1在所有细胞类型中均有较高的表达，但CYP2A13和CYP2C9未检测到表达。在所有细胞类型中也检测到介导CYP1家族诱导的芳烃（Ah）受体和Ah受体核易位子（ARNT）的表达。在MOLT-4和K562细胞中观察到CYP3A4和CYP3A5的细胞型特异性表达。在K562细胞中检测到微弱但显著的CYP3A7表达。我们在所有细胞系中检测到SULT1A1、1A3和1C2的表达，尽管SULT1B1 （U937和Jurkat）和SULT1A1 （K562）有细胞类型特异性表达。已知UGT1A家族代谢许多药物和外源药物，仅在MOLT-4和BALL-1中观察到表达。BALL-1表达8个UGT1A亚家族，MOLT-4表达2个UGT1A亚家族。所有细胞系均表达GSTA4、P1和T1，而GSTM1的表达仅在MOLT-4细胞中检测到。GSTM1被认为可以解毒香烟烟雾中的致癌物。氧化应激（过氧化氢）诱导K562细胞中CYP3A4和GSTP1的表达。化学诱导剂（对萘黄酮和3-甲基胆色素）诱导MOLT-4细胞中CYP1A1的表达。本文报道的培养细胞中药物代谢酶的概况提供了进一步了解人类血细胞中药物代谢酶的生理作用的信息。