锰超氧化物歧化酶对于细胞抵抗肿瘤坏死因子的细胞毒性至关重要。

Manganous superoxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor.

作者信息

Wong G H, Elwell J H, Oberley L W, Goeddel D V

机构信息

Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.

出版信息

Cell. 1989 Sep 8;58(5):923-31. doi: 10.1016/0092-8674(89)90944-6.

DOI:10.1016/0092-8674(89)90944-6

PMID:2476237

Abstract

Tumor necrosis factor (TNF) induces the synthesis of protein(s) that can protect cells against subsequent killing by TNF in the presence of cycloheximide. Here we demonstrate that manganous superoxide dismutase (MnSOD), a mitochondrial enzyme involved in the scavenging of superoxide radicals (O2-), is such a protein. Overexpression of MnSOD confers increased resistance to TNF plus cycloheximide on the 293 human embryonic kidney cell line. Conversely, expression of antisense MnSOD RNA renders these cells sensitive to TNF even in the absence of cycloheximide. The TNF sensitivity of the ME-180 human cervical carcinoma cell line can also be modulated through expression of sense and antisense MnSOD RNAs. These data identify MnSOD as an important determinant of cellular resistance to TNF and implicate mitochondrially generated O2- as a key component of TNF-mediated tumor cell killing.

摘要

肿瘤坏死因子（TNF）可诱导蛋白质的合成，在存在放线菌酮的情况下，这些蛋白质能保护细胞免受随后TNF介导的杀伤作用。在此我们证明，锰超氧化物歧化酶（MnSOD），一种参与清除超氧阴离子（O2-）的线粒体酶，就是这样一种蛋白质。MnSOD的过表达使293人胚肾细胞系对TNF加放线菌酮的抗性增强。相反，反义MnSOD RNA的表达使这些细胞即使在没有放线菌酮的情况下也对TNF敏感。ME-180人宫颈癌细胞系对TNF的敏感性也可通过正义和反义MnSOD RNA的表达来调节。这些数据确定MnSOD是细胞对TNF抗性的一个重要决定因素，并表明线粒体产生的O2-是TNF介导的肿瘤细胞杀伤的关键成分。