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脂质过氧化产物4-羟基壬烯醛的代谢在艾氏小鼠腹水癌细胞中取决于肿瘤年龄。

The metabolism of 4-hydroxynonenal, a lipid peroxidation product, is dependent on tumor age in Ehrlich mouse ascites cells.

作者信息

Siems W G, Grune T, Beierl B, Zollner H, Esterbauer H

机构信息

Institute of Biochemistry, Medical Faculty (Charité), Humboldt University of Berlin, Federal Republic of Germany.

出版信息

EXS. 1992;62:124-35. doi: 10.1007/978-3-0348-7460-1_13.

Abstract

4-Hydroxynonenal is a major product formed by lipid peroxidation from omega 6-polyunsaturated fatty acids as linoleic acid and arachidonic acid. This aldehyde is cytotoxic at high concentrations (in the range of 100 microM), disturbs cell proliferation at low concentrations and exhibits genotoxic effects. Furthermore, in the submicromolar range 4-hydroxynonenal is chemotactic and stimulates phospholipase C. 4-Hydroxynonenal is rapidly metabolized in eucaryotic cells. Here the metabolism of 4-hydroxynonenal was studied in suspensions of Ehrlich mouse ascites cells at different periods of the tumor age. The Ehrlich ascites tumor is a convenient biological model for the investigation of tumor cells in different age and proliferation phases of the tumor. The main products of 4-hydroxynonenal which were identified in the Ehrlich ascites cells were glutathione-HNE-conjugate, hydroxynonenoic acid and 1,4-dihydroxynonene. The formation of glutathione conjugates following the addition of 4-hydroxynonenal was higher in cells of the early phase in comparison with cells of the late phase of tumor growth. That was in accordance with the increased consumption of the reduced form of glutathione during 4-hydroxynonenal utilization. The degradation of 4-hydroxynonenal and other aldehydic products of lipid peroxidation is postulated to be an important part of the intracellular antioxidative defense system.

摘要

4-羟基壬烯醛是由ω-6多不饱和脂肪酸(如亚油酸和花生四烯酸)发生脂质过氧化反应生成的主要产物。这种醛在高浓度(100微摩尔范围内)时具有细胞毒性,在低浓度时会干扰细胞增殖并表现出基因毒性作用。此外,在亚微摩尔范围内,4-羟基壬烯醛具有趋化性并能刺激磷脂酶C。4-羟基壬烯醛在真核细胞中会迅速代谢。在此,我们研究了艾氏小鼠腹水细胞悬液在肿瘤不同生长时期对4-羟基壬烯醛的代谢情况。艾氏腹水瘤是研究处于不同年龄和增殖阶段肿瘤细胞的便捷生物学模型。在艾氏腹水细胞中鉴定出的4-羟基壬烯醛的主要产物有谷胱甘肽-HNE缀合物、羟基壬烯酸和1,4-二羟基壬烯。与肿瘤生长后期的细胞相比,在肿瘤生长早期细胞中加入4-羟基壬烯醛后谷胱甘肽缀合物的形成更多。这与4-羟基壬烯醛利用过程中还原型谷胱甘肽消耗的增加是一致的。4-羟基壬烯醛以及脂质过氧化反应产生的其他醛类产物的降解被认为是细胞内抗氧化防御系统的重要组成部分。

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