Tissue specific changes in the expression of glutamate-cysteine ligase mRNAs in mice exposed to methylmercury

Tissue specific changes in the expression of glutamate-cysteine ligase mRNAs in mice exposed to methylmercury
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DOI:
10.1016/s0378-4274(01)00341-1
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发表时间:
2001-06-20
期刊:
影响因子:
3.5
通讯作者:
Kavanagh, TJ
Kavanagh, TJ
中科院分区:
医学3区
文献类型:
--
作者:
Díaz, D;Krejsa, CM;Kavanagh, TJ

文献摘要

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谷氨酸-半胱氨酸连接酶(Glutamate-cysteine ligase,GLCL)是谷胱甘肽(glutathione,GSH)合成的限速酶,由催化亚基(glutathiate,GLCLc)和调节亚基(glutathiate,GLCLr)组成。已知这两个亚基在体外、在不同细胞类型中以及响应于各种异生物质暴露而受到差异调节。在这项研究中,我们研究了这两个亚基是否也可以在体内差异调节。我们发现,GLCLc和GLCLr的差异调节在转录水平上的组织依赖性的方式在用甲基汞(甲基汞)处理的雌性小鼠。甲基汞引起了下调的两个亚基mRNA在肝脏中:上调的两个亚基mRNA在肾脏和上调的只有催化亚基mRNA在小肠的雌性小鼠用单剂量的甲基汞(6毫克/公斤)通过腹腔注射。这些结果表明,GLCLc和GLCLr可以在体内差异调节,这种调节是组织依赖性的小鼠。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
Glutamate-cysteine ligase (GLCL), the rate-limiting enzyme in glutathione (GSH) synthesis is composed of two subunits, a catalytic (GLCLc) and a regulatory subunit (GLCLr). These two subunits are known to be differentially regulated in vitro, in different cell types and in response to various xenobiotic exposures. In this study, we examined whether these two subunits can also be differentially regulated in vivo. We found that GLCLc and GLCLr are differentially regulated at the transcriptional level in a tissue-dependent manner in female mice treated with methylmercury (MeHg). MeHg caused a downregulation of both subunit mRNAs in the liver: upregulation of both subunit mRNAs in the kidney and upregulation of only the catalytic subunit mRNA in the small intestine of female mice treated with a single dose of MeHg (6 mg/kg) by intraperitoneal injection. These results suggest that GLCLc and GLCLr can be differentially regulated in vivo, and that this regulation is tissue dependent in the mouse. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.