Constitutive mRNA expression of various glutathione S-Transferase isoforms in different tissues of mice
Constitutive mRNA expression of various glutathione S-Transferase isoforms in different tissues of mice
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DOI：
10.1093/toxsci/kfm233
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发表时间：
2007-12-01
影响因子：
3.8
通讯作者：
Klaassen, Curtis D.
中科院分区：
文献类型：
--
作者：
Knight, Tamara Raphael;Choudhuri, Supratim;Klaassen, Curtis D.
谷胱甘肽s -转移酶（Gst）酶有助于保护细胞大分子免受亲电试剂和氧化应激产物的侵害。药理学家和毒理学家主要感兴趣的是这些酶代谢癌症化疗药物、杀虫剂、除草剂和致癌物的能力。因此，Gsts的组成表达可能决定组织处理某些形式的化学应激的能力。在本研究中，研究了19种不同Gst酶在小鼠14种不同组织中的组成性mRNA表达。从本研究中获得的信息可以概括为几个基本原则：在所有检测的组织中，Gst的多个亚型都是本构性表达的；Gstk1、Gstm1、Gstm4、Gstm6和Gstt1等几个亚型在大多数研究组织中表达；至少5种Gst亚型在性腺中高表达，约3种在心脏中高表达，至少1种在大脑中高表达（Gstm5）。各种Gst亚型的表达存在明显的性别差异。除少数例外，大多数在肾脏中表达的Gst亚型在女性中的表达高于男性；心脏和性腺也有同样的趋势。至少有8种Gst亚型在胃中有高表达。这是当前研究中一个独特的发现，因为在胃肠道中高表达的药物代谢酶往往在小肠中表达最高，而在胃中表达低或不表达。综上所述，大多数Gst异构体在胃肠道和肝脏中表达最高，这强烈表明许多Gst异构体在摄入的外源性药物解毒中发挥重要作用。
Glutathione S-transferase (Gst) enzymes are instrumental in protecting cellular macromolecules against electrophiles and products of oxidative stress. Of interest primarily to pharmacologists and toxicologists is the ability of these enzymes to metabolize cancer chemotherapeutic drugs, insecticides, herbicides, and carcinogens. Thus, constitutive expression of Gsts might determine a tissue's ability to handle certain forms of chemical stress. In the present study, the constitutive mRNA expression of 19 different Gst enzymes was investigated in 14 different tissues in mice. The information obtained from the present study could be distilled into a few generalized principles: in all tissues examined, multiple isoforms of Gst were constitutively expressed; several isoforms, such as Gstk1, Gstm1, Gstm4, Gstm6, and Gstt1, were expressed in most of the tissues studied; at least five Gst isoforms were highly expressed in the gonads, about three in heart, and at least one in brain (Gstm5). Gender differences in the expression of various Gst isoforms were pronounced. With a few exceptions, most of the Gst isoforms expressed in kidney showed higher expression in females than males; the same trend was observed for heart and gonads. At least eight Gst isoforms showed very high expression in stomach. This was a unique finding in the current study because drug-metabolizing enzymes that are highly expressed in the gastrointestinal (GI) tract tend to have the highest expression in small intestine with low or no expression in the stomach. In summary, most Gst isoforms are most highly expressed in the GI tract and liver, which strongly suggests an important role of many Gst isoforms in detoxification of ingested xenobiotics.