Glycine N-methyltransferase is a mediator of cytochrome P4501A1 gene expression.
Glycine N-methyltransferase is a mediator of cytochrome P4501A1 gene expression.
复制标题
甘氨酸 N-甲基转移酶是细胞色素 P4501A1 基因表达的介质。
DOI：
10.1006/abbi.1995.1480
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Bresnick,E
中科院分区：
文献类型：
--
作者：
Raha,A;Joyce,T;Gusky,S;Bresnick,E
细胞色素 P4501A1 是诱导条件下最接近芳烃羟化酶活性的同工酶，被认为受到多种反式作用因子的调节，包括 4S 多环芳烃结合蛋白；该蛋白质最近被鉴定为甘氨酸N-甲基转移酶（Raha 等人 (1994) J. Biol. Chem. 269, 5750-5756）。先前的研究表明，含有 4S 结合蛋白的部分纯化的肝脏制剂与细胞色素 P4501A1 基因的 5' 侧翼区域相互作用。因此，进一步研究了 4S 结合蛋白作为细胞色素 P4501A1 基因调节介质的能力。通过脂质转染将甘氨酸 N-甲基转移酶 cDNA 的反义 24 聚体寡核苷酸引入大鼠肝癌 H4IIE 细胞中，与有义和乱序反义寡核苷酸对照相比，苯并 (a) 芘介导的乙氧基试卤灵-O-脱乙基酶活性和蛋白质的诱导减少了 60%。此外，反义寡核苷酸导致细胞色素P4501A1 mRNA的稳态水平显着降低。使用有义寡核苷酸没有观察到这样的效果。通过链球菌溶血素-O 透化技术将 GNMT 多克隆抗体引入 H4IIE 细胞，显着降低苯并（a）芘结合和苯并（a）芘诱导的乙氧基试卤灵-O-脱乙基酶活性，但对 2,3,7,8-四氯二苯并-对二恶英诱导没有影响。总的来说，这些发现表明，除了 Ah（二恶英）受体之外，甘氨酸 N-甲基转移酶似乎既是多环芳烃结合蛋白，又是多环烃（如苯并（a）芘）诱导细胞色素 P4501A1 基因的介体。
Cytochrome P4501A1, the isozyme most closely approximating aryl hydrocarbon hydroxylase activity under conditions of induction, is thought to be regulated by several trans-acting factors, including the 4S polycyclic aromatic hydrocarbon-binding protein; this protein has recently been identified as glycine N-methyltransferase (Raha et al. (1994) J. Biol. Chem. 269, 5750-5756). Previous studies had shown that partially purified liver preparations containing the 4S binding protein interacted with 5′-flanking regions of the cytochrome P4501A1 gene. Consequently, the ability of the 4S binding protein to serve as a mediator in the regulation of the cytochrome P4501A1 gene was investigated further. Introduction of an antisense 24-mer oligonucleotide to glycine N-methyltransferase cDNA into rat hepatoma H4IIE cells by lipofectin resulted in a 60% reduction in the benzo(a)pyrene-mediated induction of ethoxyresorufin-O-deethylase activity and protein over the sense and scrambled antisense oligonucleotide controls. In addition, the antisense oligonucleotide caused a marked reduction in the steady-state level of cytochrome P4501A1 mRNA; no such effect was observed with the sense oligonucleotide. Introduction of GNMT polyclonal antibodies into H4IIE cells by a streptolysin-O permeabilization technique markedly reduced both benzo(a)pyrene-binding and benzo(a)pyrene-induced ethoxyresorufin-O-deethylase activities, but had no effect on 2,3,7,8-tetrachlorodibenzo-p-dioxin induction. Collectively, these findings suggest that, in addition to the Ah (dioxin) receptor, glycine N-methyltransferase appears to be both a polycyclic aromatic hydrocarbon-binding protein and a mediator of the induction of the cytochrome P4501A1 gene by polycyclic hydrocarbons such as benzo(a)pyrene.