Inhibition of target cell mitochondrial electron transfer by tumor necrosis factor

FEBS Letters

Laster, Scott M.¹  Lancaster, Jack R.¹  Gooding, Linda R.¹ 

[1] Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA

关键词: Tumor necrosis factor-α;    Cytotoxicity;    immunological;    Bioenergetics;    Mitochondria;    Electron transport;    (Murine fibroblast);    hrTNF;    human recombinant tumor necrosis factor-α;    TMPD;    tetramethylphenylenediamine;    FCCP;    carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone;    CHX;    cycloheximide;   

DOI  :  10.1016/0014-5793(89)80454-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Using digitonin permeabilization to assay mitochondrial electron transfer, we have found that respiratory activity (succinoxidase and cytochrome oxidase) in three mouse fibroblast lines is completely eliminated by incubation with human recombinant tumor necrosis factor-α (hrTNF). As with cytotoxicity, hrTNF-induced mitochondrial dysfunction occurs in resistant cells upon inhibition of protein synthesis, whereas sensitive cells exhibit spontaneous respiratory inhibition. In C3HA cells, inhibition is detectable 1.5–2 h after hrTNF addition, preceding cell lysis by at least 5 h (as measured by dye exclusion), and is approximately coincidental with morphological changes we have previously reported for this cell line. LM cells also exhibit inhibition of electron transfer, coincidental with morphological changes. These results suggest that bioenergetic dysfunction may be involved in the cytotoxic mechanism of TNF.

【 授权许可】

Unknown