Characterization, localization and regulation of a novel phenobarbital-inducible form of cytochrome P450, compared with three further P450-isoenzymes, NADPH P450-reductase, glutathione transferases and microsomal epoxide hydrolase.
Characterization, localization and regulation of a novel phenobarbital-inducible form of cytochrome P450, compared with three further P450-isoenzymes, NADPH P450-reductase, glutathione transferases and microsomal epoxide hydrolase.
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与另外三种 P450 同工酶、NADPH P450 还原酶、谷胱甘肽转移酶和微粒体环氧化物水解酶相比，新型苯巴比妥诱导形式的细胞色素 P450 的表征、定位和调节。
作者：
C. Wolf;E. Moll;T. Friedberg;F. Oesch;A. Buchmann;W. Kuhlmann;H. Kunz
从苯巴比妥处理的大鼠肝脏中分离出两种细胞色素P450（PB 1和PB 2）。PB2（mol.重量53 500）是新的，并且是在447 nm处具有Soret峰的苯巴比妥诱导酶的第一个实例。使用酶联免疫吸附试验，一些免疫化学和结构的相似性，观察这些细胞色素之间。PB 1和PB 2诱导苯巴比妥，Aroclor 1254，反式二苯乙烯氧化物和在较小程度上由异黄樟油素。这些蛋白质在未经处理的大鼠的肝脏中的免疫组织化学定位显示PB 1被定位在一个大的区域和PB 2在中央静脉周围的细胞的狭窄范围。这表明肝细胞的异质性，即使在小叶中心区，并表明这两种蛋白质的合成调节不同，虽然都是由相同的代理，苯巴比妥诱导。两种3-甲基胆蒽诱导的细胞色素MC 1（mol.重量54 500）和MC 2（mol.重量MC 2主要分布在门静脉周围区，但也弥漫分布于整个小叶，包括一些小叶中心细胞，MC 1集中在小叶中心区。谷胱甘肽转移酶（GST）的两个主要群体的定位也是不同的。“C”型蛋白质（Yb B Yb“）和微粒体环氧化物水解酶（EH）集中分布在中央静脉周围，而”B“型蛋白质（Ya Yc）和细胞色素P450还原酶分布在该区域的较大区域。因此，同一个酶家族的某些成员的定位是不同的，而跨家族边界的定位存在相似之处：（i）PB 2、MC 1、EH和GST 'C'型蛋白集中在中央静脉周围的狭窄区域，（ii）PB 1和GST 'B'型蛋白占据大的小叶中心区域，（iii）PB 2、MC 1、EH和GST 'C'型蛋白集中在中央静脉周围的狭窄区域，（iv）PB 1和GST 'B'型蛋白集中在中央静脉周围的狭窄区域。（iii）MC 2水平非常低，主要分布在门静脉周围，但也弥漫分布在整个小叶。用诱导剂处理动物增加了染色强度，并且在一些情况下将含有这些蛋白质的细胞区域扩展到相邻区域，而不会从根本上改变它们的分布。然而，β-萘酚酮治疗导致MC 1转移到门静脉周围区域。这表明这些蛋白质在某些细胞中的表达不是不可逆的分化质量，而是取决于调节组分的抑制和去抑制程度。（400字处截断摘要）
Two cytochromes P450 (PB1 and PB2) have been isolated from the livers of rats treated with phenobarbital. PB2 (mol. wt. 53 500) is novel and is the first example of a phenobarbital-inducible enzyme with a Soret peak at 447 nm. Using an enzyme-linked immunosorbent assay, some immunochemical and structural similarities were observed between these cytochromes. PB1 and PB2 were induced by phenobarbital, Aroclor 1254, trans-stilbene oxide and to a lesser extent by isosafrole. Immunohistochemical localization of these proteins in the liver of untreated rats showed PB1 to be localized in a large area and PB2 in a narrow range of cells around the central vein. This demonstrates the heterogeneity of hepatocytes even within the centrilobular area and indicates that the synthesis of these two proteins is regulated differently although both are induced by the same agent, phenobarbital. Two 3-methylcholanthrene inducible cytochromes MC1 (mol. wt. 54 500) and MC2 (mol. wt. 57 000) were present at very low levels, MC2 mostly in the periportal region but also diffusely distributed throughout the lobule including some centrilobular cells, MC1 concentrated in the centrilobular region. The localization of two major groups of glutathione transferases (GST's) was also different. 'C' type proteins (Yb Yb') and microsomal epoxide hydrolase (EH), were concentrated around the central vein, whereas the 'B' type proteins (Ya Yc) and cytochrome P450 reductase were distributed in a larger area of this region. Thus, the localization was different for some members of the same enzyme family, whilst similarities in the localization existed across the border of the families: (i) PB2, MC1, EH and GST 'C' type proteins were concentrated in a narrow area around the central vein; (ii) PB1 and GST 'B' type proteins occupied a large centrilobular area; (iii) MC2 levels were very low, predominantly periportal but also diffusely distributed throughout the lobule. Treatment of the animals with inducers increased the staining intensity and in several cases extended the areas of cells containing these proteins over the adjacent zone without fundamentally altering their distributions. However, treatment with beta-naphthoflavone led to a shift of MC1 to the periportal area. This suggests that the expression of these proteins in certain cells is not an irreversible quality of differentiation but depends on the degree of suppression and derepression of regulatory components.(ABSTRACT TRUNCATED AT 400 WORDS)
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影响因子：
2.9
作者：
GUENGERICH, FP;DANNAN, GA;KAMINSKY, LS
通讯作者：
KAMINSKY, LS
大鼠肝微粒体的苯并(a)芘代谢：添加纯化的谷胱甘肽 S-转移酶 A、B 和 C 的影响。
影响因子：
11.2
作者：
Morgenstern,R;Guthenberg,C;Mannervik,B;DePierre,JW;Ernster,L
通讯作者：
Ernster,L
对未经治疗的大鼠肝脏内苯巴比妥和 3-甲基胆蒽诱导细胞色素 P-450 的定位和分布进行免疫组织化学研究。
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Baron,J;Redick,JA;Guengerich,FP
通讯作者：
Guengerich,FP
3-甲基胆蒽、β-萘黄酮和苯巴比妥对小叶中心、中带和汇管周围肝细胞内细胞色素 P-450 3-甲基胆蒽诱导同工酶的影响。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Baron,J;Redick,JA;Guengerich,FP
通讯作者：
Guengerich,FP
2,3,7,8-四氯二苯并-对二恶英和苯巴比妥对兔肾、肺和肝中四种细胞色素 P-450 同工酶的出现和分布的影响。
影响因子：
11.2
作者：
Dees,JH;Masters,BS;Muller-Eberhard,U;Johnson,EF
通讯作者：
Johnson,EF