[Correlation of cytotoxic activity of mutant forms of tumor necrosis factor alpha with changes in the level of free sphingosine in murine liver].
Sphingosine, the product of enzymatic degradation of sphingomyelin, displays a high cytotoxic activity and is accumulated in animal organs under the action of the tumour necrosis factor (TNF alpha). To elucidate the role of sphingosine in the realization of TNF cytotoxicity, TNF mutants were obtained which differed in their cytotoxic action on L929 cells. The wild strain of TNF and the mutant having a deletion in position 67-71 displayed the highest toxicity and sharply stimulated sphingosine accumulation in mouse hepatocytes. A moderate increase in the sphingosine content was induced by mutants with point and double mutations in positions E127Q, I155L and V150I displaying a much lower toxicity in comparison with the wild strain. The toxic, mutagenic and antimutagenic activities of sphingosine were investigated. Despite the high degree of cytotoxicity, sphingosine did not display any mutagenic activity but had a pronounced antimutagenic effect on E. coli cells. The role of phospholipid enzymatic degradation products in activation of sphingomyelin cycle enzymes stimulating of sphingosine accumulation in animal cells under the action of TNF alpha is discussed.
Solov'ev
A S
AS
Korobko
V G
VG
Shingarova
L N
LN
Vasil'eva
S V
SV
Makhova
E V
EV
Alesenko
A V
AV
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D004926:Escherichia coli / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D051381:Rats; D017384:Sequence Deletion; D013110:Sphingosine / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*
D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha; D013110:Sphingosine
Korreliatsiia tsitotoksicheskoĭ aktivnosti mutantnykh form faktora nekroza opukholeĭ-alpha s izmeneniem urovnia svobodnogo sfingozina v pecheni mysheĭ.