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Inhibition of target cell mitochondrial electron transfer by tumor necrosis factor
Author(s) -
Lancaster Jack R.,
Laster Scott M.,
Gooding Linda R.
Publication year - 1989
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(89)80454-5
Subject(s) - mitochondrion , chemistry , tumor necrosis factor alpha , electron transfer , cell , microbiology and biotechnology , biophysics , biochemistry , biology , photochemistry , immunology
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.