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干扰素对小鼠谷胱甘肽转移酶的诱导与抑制作用

Induction and suppression of glutathione transferases by interferon in the mouse.

作者信息

Adams D J, Balkwill F R, Griffin D B, Hayes J D, Lewis A D, Wolf C R

出版信息

J Biol Chem. 1987 Apr 5;262(10):4888-92.

PMID:3558375
Abstract

The administration of interferon-alpha/beta to female nude (nu/nu) mice caused significant changes in the levels of the cytosolic hepatic glutathione transferases. Antibodies raised against rat subunits, Ya, Yc, Yb1, Yb2, and Yk, and the subunits of the human transferases, mu (YbYb), lambda (YfYf), and epsilon (B1B1) all reacted with enzymes in the mouse and were used to demonstrate suppression and induction of transferase levels. Western blot analysis followed by semiquantitation by laser scanning showed the Ya, Yb1, Yb2, Yc, Yk, mu, and B1 subunits to be suppressed by 11, 11, 44, 30, 12, 14, and 47%, respectively, by interferon treatment. In contrast to these findings, the Yf subunit was induced 5-7-fold. A concomitant 220% increase was observed in the specific activity of the hepatic cytosol for ethacrynic acid, a substrate for the Yf subunit. Changes in the levels of transferase enzymes in normal and tumor cells may have significant implications when cytotoxic drugs are used in combination with interferons in cancer therapy. The Yf subunit, an enzyme found in human tumors and in placenta (Polidoro, G., Di Mio, C., Del Boccio, G., Zulli, P., and Fererici, G. (1980) Biochem. Pharmacol. 29, 1677-1680) has also been shown to be elevated in hepatic preneoplastic lesions (Kitahara, A., Satoh, K., Nishimura, K., Ishikawa, T., Ruike, K., Sato, K., Tsuda, H., and Ito, N. (1984) Cancer Res. 44, 2698-2703). These data indicate that the Yf subunit represents a potentially important interferon-inducible gene product.

摘要

对雌性裸(nu/nu)鼠给予α/β干扰素后,肝脏胞质谷胱甘肽转移酶水平发生了显著变化。用针对大鼠亚基Ya、Yc、Yb1、Yb2和Yk以及人转移酶亚基μ(YbYb)、λ(YfYf)和ε(B1B1)制备的抗体与小鼠体内的酶发生反应,并用于证明转移酶水平的抑制和诱导。蛋白质印迹分析后通过激光扫描进行半定量显示,经干扰素处理后,Ya、Yb1、Yb2、Yc、Yk、μ和B1亚基分别被抑制了11%、11%、44%、30%、12%、14%和47%。与这些结果相反,Yf亚基被诱导了5至7倍。观察到肝脏胞质中Yf亚基底物依他尼酸的比活性相应增加了220%。当细胞毒性药物与干扰素联合用于癌症治疗时,正常细胞和肿瘤细胞中转移酶水平的变化可能具有重要意义。Yf亚基是一种在人类肿瘤和胎盘中发现的酶(波利多罗,G.,迪·米奥,C.,德尔·博乔,G.,祖利,P.,和费雷里西,G.(1980年)《生物化学与药理学》29卷,1677 - 1680页),在肝脏癌前病变中也已显示其水平升高(北原,A.,佐藤,K.,西村,K.,石川,T.,留井,K.,佐藤,K.,津田,H.,和伊藤,N.(1984年)《癌症研究》44卷,2698 - 2703页)。这些数据表明Yf亚基代表一种潜在重要的干扰素诱导基因产物。

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引用本文的文献

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Mol Vis. 2011;17:2507-15. Epub 2011 Sep 27.
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Inhibition of cell proliferation and glutathione S-transferase by ascorbyl esters and interferon in mouse glioma.抗坏血酸酯和干扰素对小鼠胶质瘤细胞增殖及谷胱甘肽S-转移酶的抑制作用
J Neurooncol. 1993 Apr;16(1):1-10. doi: 10.1007/BF01324828.
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Biochem J. 1989 Nov 1;263(3):679-85. doi: 10.1042/bj2630679.
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