A possible involvement of endogenous polyamines in the TNF-α cellular sensitivity

AbstractA critical step in the cytotoxic action mechanism of tumor necrosis factor-α (TNF-α) involves, among mitochondrial dysfunctions, an early change of the inner membrane permeability displaying the characteristics of permeability transition. Cytosolic polyamines, especially spermine, are known to inhibit it. Our results show that spermine is only detectable in the TNF-α resistant C6 cells while N1-acetylspermidine is present in the TNF-α sensitive WEHI-164 cells, and putrescine and spermidine are found in both. TNF-α treatment does not change this distribution but only induces a quantitative alteration in TNF-α sensitive cells. Omission of glutamine (energetic substrate) from the culture media alters neither the TNF-α responsiveness of both cell lines nor their polyamine distributions, only their quantitative polyamine contents