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

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作者：

GHW Wong，JH Elwell，LW Oberley，DV Goeddel

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摘要：

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 manganeous superoxide dismutase (MnSOD), a mitochondrial enzyme involved in the scavenging of superoxide radicals (O 2), 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 O 2 as a key component of TNF-mediated tumor cell killing.

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关键词：

LGIC SUPERFAMILY PROTO-BINDING SITE CYS-LOOP MOTIF DOCKING MODEL ANIONIC SITE SPECIFICITY RESIDUE

DOI：

10.1016/0092-8674(89)90944-6

被引量：

2378

年份：

1989