The distribution of Theta-class glutathione S-transferases in the liver and lung of mouse, rat and human
The distribution of Theta-class glutathione S-transferases in the liver and lung of mouse, rat and human
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DOI：
10.1042/bj3180297
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发表时间：
1996-08-15
影响因子：
4.1
通讯作者：
Green, T
中科院分区：
文献类型：
--
作者：
Mainwaring, GW;Williams, SM;Green, T
两个鼠Theta类谷胱甘肽S-转移酶（GST），mGSTT 1和mGSTT 2，已被克隆和测序。鼠cDNA与大鼠和人酶的公开序列一起用于设计寡核苷酸探针，以确定这些酶在大鼠、小鼠和人的肝和肺中的mRNA分布。mRNA的分布进行了比较，用大鼠GSTT 2 -2的抗体测定的酶蛋白。抗体和寡核苷酸探针的分布模式相同。两种酶在小鼠组织中的浓度均显著高于大鼠或人体组织。在小鼠肝脏中，这两种酶都定位于特定的细胞类型和细胞核中。虽然GSTT 2 -2在大鼠肝脏中的分布与在小鼠中观察到的相似，但GSTT 1 -1并不定位于特定的细胞类型或大鼠或人肝脏的细胞核中。在肺中，非常高浓度的Theta酶存在于小鼠肺Clara细胞和纤毛细胞中，仅在大鼠肺的Clara细胞中的水平低得多。在肺泡/细支气管交界处的少量Clara细胞和纤毛细胞中检测到低水平的人转移酶GSTT 1 -1。物种之间的相对活性，以及每个物种的肝脏和肺部内的细胞和亚细胞分布，为二氯甲烷的物种特异性提供了解释，二氯甲烷是一种由谷胱甘肽S-转移酶GSTT 1 -1激活的小鼠特异性致癌物。
Two murine Theta-class glutathione S-transferases (GSTs), mGSTT1 and mGSTT2, have been cloned and sequenced. The murine cDNAs, together with the published sequences of the rat and human enzymes, were used to design oligonucleotide probes in order to determine the distribution of mRNA for these enzymes in the liver and lung of rat, mouse and human. The mRNA distribution was compared with that of enzyme protein determined with an antibody to rat GSTT2-2. Both the antibody and the oligonucleotide probes gave the same distribution patterns. Both enzymes were present at significantly higher concentrations in mouse tissues than in rat or human tissues. In mouse liver, both enzymes were localized in specific cell types and in nuclei. Although the distribution of GSTT2-2 in rat liver was similar to that seen in the mouse, GSTT1-1 was not localized in a specific cell type or in the nuclei of either rat or human liver. In the lungs, very high concentrations of the Theta enzymes were present in mouse-lung Clara cells and ciliated cells, with much lower levels in the Clara cells only of rat lung. Low levels of human transferase GSTT1-1 were detected in a small number of Clara cells and ciliated cells at the alveolar/bronchiolar junction. The relative activities between species, and the cellular and sub-cellular distribution within the liver and lungs of each species, provides an explanation for the species-specificity of methylene chloride, a mouse-specific carcinogen activated by glutathione S-transferase GSTT1-1.