Structure and physiological function of human and rat glutathione S-transferase

人和大鼠谷胱甘肽S-转移酶的结构和生理功能

• 批准号: 60570104
• 负责人: SATOH Kimihiko
• 金额: $ 1.02万
• 依托单位: Hirosaki Univ. Sch. Med.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60570104/
• 关键词: Glutathione-transferase; Isozyme; Glutathione; 化学発癌

Multiple molecular forms of hepatic glutathione S-transferase (GST) were purified from three animal species. Among the 5 human GSTs (I-V) separated on chromatofocusing, type II was the hybrid of I and IV and type V was identical with the placental GST- <pi> . Of the four subunits (Ya, Yb, Yc and Yp) consisting the seven dimeric rat GSTs ( <L_2> , BL, <B_2> , <A_2> , AC, <C_2> , <P_2> ), Yb was separated into two species (Yb, Yb') which, together with Yp, were further composed of two microspecies differing 0.3 unit in their isoelectric points on two-dimensional gel electrophoresis. Only three major forms (I-III) were present in male mouse liver. Despite that human (V), rat ( <P_2> , GST-P) and mouse (II) were closely related in substrate specificities, N-terminal amino acid sequences and immunological crossreactivities, the former two existed in very low amounts in respective livers, whereas mouse II was the predominant in the male liver, where the expression was, strikingly, controlled … More by testosterone. Following our finding that the polypeptide which was most markedly increased in preneoplastic rat livers induced by administration of diethylnitrosamine and 2-fluorenylacetamide was identical with the subunit of placental GST-P together with the immunohistochemical demonstration of its specific localization in the enzyme-altered foci, we have established the purification method from the preneoplastic tissue. Foci were also inducible in rat livers by other carcinogens but not by noncarcinogens with minor exceptions. Single and multiple cells positive for GST-P were detectable in rat livers several days after administration of diethylnitrosamine, suggesting that the microscopic cells are possible precursors of the foci. GST-P had an additional peroxidase activity to detoxicate organic hydroperoxides. furthermore, it showed enantioselective GSH-conjugating activity for 9,10-dihydroxybenzo a pyrene 7,8-oxide. GST-P could be an excellent marker enzyme in the analysis of carcinogenic processes due to its specificity and the extraordinary high immunohistochemical sensitivity for the preneoplastic cells. Less

从三种动物中纯化了多种分子形式的肝谷胱甘肽S-转移酶（GST）。在5个人GST（I-V）中，Ⅱ型为Ⅰ型和Ⅳ型的杂合体，Ⅴ型与胎盘GST-一致。<pi>在由7个二聚体GST组成的4个亚基（Ya，Yb，Yc和Yp）中，Yb被分成2个亚基（Yb，Yb '），它们与Yp一起进一步由2个微亚基组成，在双向凝胶电泳上它们的等电点相差0.3个单位。<L_2><B_2><A_2><C_2><P_2>雄性小鼠肝脏中仅存在三种主要形式（I-III）。尽管人（V）、大鼠（，GST-P）和小鼠（II）在底物特异性、N末端氨基酸序列和免疫交叉反应性方面密切相关，但前两者在各自肝脏中的含量非常低，而小鼠II在雄性肝脏中占主导地位，其中表达受到显着控制<P_2> ...更多信息 睾丸激素。在我们发现由二乙基亚硝胺和2-芴基乙酰胺诱导的癌前大鼠肝脏中最明显增加的多肽与胎盘GST-P亚基相同，并通过免疫组织化学证明其在酶改变的病灶中的特异性定位之后，我们建立了从癌前组织中纯化的方法。病灶也诱导在大鼠肝脏中的其他致癌物，但不是由非致癌物有轻微的例外。单细胞和多细胞GST-P阳性检测大鼠肝脏给药后几天，二乙基亚硝胺，表明显微镜下的细胞可能是前体的病灶。GST-P具有额外的过氧化物酶活性，以解毒有机氢过氧化物。此外，它对9，10-二羟基苯并[a]芘7，8-氧化物显示出对映选择性的GSH-缀合活性。GST-P对癌前病变细胞具有特异性和极高的免疫组化敏感性，是一种很好的致癌过程分析的标记酶。少

项目成果

佐藤清美: 癌と化学療法. (1987)

佐藤清美：癌症与化疗（1987）。

Masae Tatematsu: Carcinogenesis. 6. 1621-1625 (1985)

立松正江：致癌作用。

Kimihiko Satoh et al.: "Purification, induction and distribution of placental glutathione transferase : A new marker enzyme for preneoplastic cells in the rat chemical hepatocarcinogenesis." Proceedings of the National Academy of Sciences U. S. A.82. 3964

Kimihiko Satoh 等人：“胎盘谷胱甘肽转移酶的纯化、诱导和分布：大鼠化学肝癌发生过程中癌前细胞的一种新标记酶。”

Kiyomi Sato et al.: T.J. Mantle, C.B. Pickett and J.D. Hayes., Taylor & Francis Ltd., London. Placental glutathione S-transferase as a marker for (pre)neoplastic tissues. in "Glutathione and carcinogenesis"., (1987)

佐藤清美等人：T.J.

Kimihiko Satoh: Proceedings of the National Academy of Science U.S.A.82. 3964-3968 (1985)

佐藤公彦：美国国家科学院院刊82。