A POSSIBLE INVOLVEMENT OF ENDOGENOUS POLYAMINES IN THE TNF-ALPHA CELLULAR-SENSITIVITY

A critical step in the cytotoxic action mechanism of tumor necrosis fa ctor-alpha (TNF-alpha) involves, among mitochondrial dysfunctions, an early change of the inner membrane permeability displaying the charact eristics of permeability transition. Cytosolic polyamines, especially spermine, are known to inhibit it. Our results show that spermine is o nly detectable in the TNF-alpha resistant C6 cells while N1-acetylsper midine is present in the TNF-alpha sensitive WEHI-164 cells, and putre scine and spermidine are found in both. TNF-alpha treatment does not c hange this distribution but only induces a quantitative alteration in TNF-alpha sensitive cells, Omission of glutamine (energetic substrate) from the culture media alters neither the TNF-alpha responsiveness of both cell lines nor their polyamine distributions, only their quantit ative polyamine contents. (C) 1998 Federation of European Biochemical Societies.