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肾细胞癌和肾组织中的谷胱甘肽S-转移酶同工酶与谷胱甘肽

Glutathione S-transferase isoenzymes and glutathione in renal cell carcinoma and kidney tissue.

作者信息

Gajewska J, Szczypka M, Pych K, Borówka A, Laskowska-Klita T

机构信息

Department of Biochemistry, National Research Institute of Mother and Child, Warsaw, Poland.

出版信息

Neoplasma. 1995;42(4):167-72.

PMID:7659181
Abstract

Many studies have established the role of the glutathione S-transferases (GSTs) and glutathione (GSH) in the neoplastic process and the drug resistance of tumor. Using isoelectric focusing we separated different forms of GSTs in 28 renal cell carcinomas (RCCs) and in morphologically unchanged adjacent kidney. In addition we determined in RCCs and adjacent kidney the level of GSH and the activities of enzymes participating in synthesis and uptake of this thiol compound. We found higher activity of acidic GSTs and higher level of GSH in RCCs versus kidney. Therefore we suggest that both parameters may play the significant role in the well known phenomenon of intrinsic cytostatic drug resistance of RCC. We also observed the elevation of GSH synthetase activity in tumor tissues in comparison to the kidneys. It may indicate that GSH synthetase, catalysing the final step in GSH synthesis, may participate in the elevation of GSH concentration in RCCs. In this work we also compared the tested parameters in RCCs in relation to the size and local extent of primary tumor (T). We found significantly lower activity of gamma-glutamyl transpeptidase (GGT) as well as GSH synthetase in the group of T3 and T4 tumors than in T2 tumors. However, no substantial differences in GSH concentrations were observed between these distinguished groups.

摘要

许多研究已证实谷胱甘肽S-转移酶(GSTs)和谷胱甘肽(GSH)在肿瘤形成过程及肿瘤耐药性中的作用。我们采用等电聚焦法,在28例肾细胞癌(RCCs)及形态未改变的癌旁肾组织中分离出不同形式的GSTs。此外,我们还测定了RCCs及癌旁肾组织中GSH的水平以及参与该硫醇化合物合成和摄取的酶的活性。我们发现,与肾组织相比,RCCs中酸性GSTs的活性更高,GSH的水平也更高。因此,我们认为这两个参数可能在RCCs众所周知的内在细胞毒性药物耐药现象中起重要作用。我们还观察到,与肾组织相比,肿瘤组织中GSH合成酶的活性有所升高。这可能表明,催化GSH合成最后一步的GSH合成酶可能参与了RCCs中GSH浓度的升高。在这项研究中,我们还比较了RCCs中与原发肿瘤(T)大小和局部范围相关的检测参数。我们发现,T3和T4期肿瘤组中的γ-谷氨酰转肽酶(GGT)以及GSH合成酶的活性显著低于T2期肿瘤组。然而,在这些不同组之间未观察到GSH浓度的实质性差异。

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