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长期低剂量γ射线辐照后小鼠脾脏中新的谷胱甘肽合成途径的激活。

Activation of de novo GSH synthesis pathway in mouse spleen after long term low-dose γ-ray irradiation.

机构信息

Research Center, Dongnam Institute of Radiological and Medical Science , 40 Jwadong-gil, Jangan-eup, Gijang-gun, Busan, Republic of Korea.

出版信息

Free Radic Res. 2013 Feb;47(2):89-94. doi: 10.3109/10715762.2012.747678. Epub 2012 Nov 27.

DOI:10.3109/10715762.2012.747678
PMID:23136969
Abstract

Glutathione (GSH) is an important cellular antioxidant and has a critical role in maintaining the balance of cellular redox. In this study, we investigated the GSH biosynthesis genes involved in the elevation of endogenous GSH levels using an irradiation system with an irradiation dose rate of 1.78 mGy/h, which was about 40,000 times less than the dose rates used in other studies. The results showed that GSH levels were significantly increased in the low-dose (0.02 and 0.2 Gy) irradiated group compared to those in the non-irradiated group, but enzymatic antioxidants such as superoxide dismutase and catalase were not induced at any doses tested. The elevation in GSH was accompanied by elevated expression of glutamate-cysteine ligase modifier subunit, but no changes were observed in the expression of glutamate-cysteine ligase catalytic subunit and thioredoxin in de novo GSH synthesis. In the case of genes involved in the GSH regeneration cycle, the expression of glutathione reductase was not changed after irradiation, whereas glutathione peroxidase was only increased in the 0.2 Gy irradiated group. Collectively, our results suggest that the de novo pathway, rather than the regeneration cycle, may be mainly switched on in response to stimulation with long-term low-dose radiation in the spleen.

摘要

谷胱甘肽 (GSH) 是一种重要的细胞内抗氧化剂,在维持细胞氧化还原平衡方面起着关键作用。在这项研究中,我们使用辐射剂量率为 1.78 mGy/h 的辐照系统研究了参与内源性 GSH 水平升高的 GSH 生物合成基因,该剂量率比其他研究中使用的剂量率低约 40000 倍。结果表明,与未辐照组相比,低剂量 (0.02 和 0.2 Gy) 辐照组的 GSH 水平显著升高,但在测试的任何剂量下,酶抗氧化剂如超氧化物歧化酶和过氧化氢酶均未被诱导。GSH 的升高伴随着谷氨酸-半胱氨酸连接酶修饰亚基表达的升高,但在从头合成 GSH 中,谷氨酸-半胱氨酸连接酶催化亚基和硫氧还蛋白的表达没有变化。在 GSH 再生循环涉及的基因中,辐照后谷胱甘肽还原酶的表达没有变化,而谷胱甘肽过氧化物酶仅在 0.2 Gy 辐照组中增加。总之,我们的结果表明,从头途径而不是再生循环可能主要在长期低剂量辐射刺激脾脏时被激活。

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