Expression of glutamate-cysteine ligase during mouse development

Expression of glutamate-cysteine ligase during mouse development
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DOI:
10.1002/mrd.10076
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发表时间:
2002-05-01
影响因子:
2.5
通讯作者:
Kavanagh, TJ
Kavanagh, TJ
中科院分区:
生物学3区
文献类型:
--
作者:
Díaz, D;Krejsa, CM;Kavanagh, TJ

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三肽谷胱甘肽(GSH)在保护细胞免受氧化应激方面起着至关重要的作用,其合成分为两步。限速步骤是谷氨酸和半胱氨酸的结合,其由酶谷氨酸-半胱氨酸连接酶(GCL)催化。这种酶由两个亚基组成:一个大的催化亚基(GCLc)和一个较小的修饰亚基(GCLm),它们来自不同的基因。细胞GSH水平的控制对正常发育至关重要。在目前的研究中,我们研究了Gclc和Gclm转录本,以及GCLc蛋白,在发育中的小鼠胚胎的组织分布。我们发现,这两种mRNA在妊娠第10天(gd 10)和gd 12在肝脏和CNS中高度表达,Gclm在肝脏中比Gclc相对于其他组织更丰富。此外,这两个亚基mRNA的表达在胚胎中并不总是平行的,因为一些组织优先表达其中一个亚基,这表明这两个基因在小鼠发育过程中差异表达。GCLc蛋白在整个胚胎中也广泛表达,并且通常与Gclc mRNA共定位。(C)2002 Wiley-Liss,Inc.
The tripeptide glutathione (GSH), which plays a crucial role in protecting cells against oxidative stress, is synthesized in a two-step process. The rate-limiting step is the binding of glutamate and cysteine, which is catalyzed by the enzyme glutamate-cysteine ligase (GCL). This enzyme is composed of two subunits: a large catalytic subunit (GCLc) and a smaller modifying subunit (GCLm), originating from different genes. Control of cellular GSH levels is essential for normal development. In the current study, we investigated the tissue distribution of Gclc and Gclm transcripts, as well as GCLc protein, in the developing mouse embryo. We found that both mRNAs were highly expressed in the liver and CNS at gestational day 10 (gd 10) and gd 12, with Gclm being more abundant than Gclc in the liver relative to other tissues. Also, the expression of the two subunit mRNAs was not always parallel in the embryo, in that some tissues expressed one of the subunits preferentially, suggesting that the two genes are differentially expressed during mouse development. The GCLc protein was also widely expressed throughout the embryo, and, in general, it co-localized with the Gclc mRNA. (C) 2002 Wiley-Liss, Inc.