Av. Alessenko et al., Role of endogenous TNF-alpha and sphingosine in induced DNA synthesis in regenerating rat liver after partial hepatectomy, BIOCHEM-MOS, 64(8), 1999, pp. 890-895
Cytokine-stimulated metabolism of sphingomyelin results in the accumulation
of ceramide and sphingosine which play a part in the regulation of cell pr
oliferation, differentiation, and reception, as well as in oncogenesis. For
mation of TNF-alpha (a member of the cytokine family), accumulation of sphi
ngosine, and DNA synthesis (measured by immunoblotting, HPLC, and [H-3]thym
idine incorporation, respectively) were studied in rat liver after partial
hepatectomy. The content of TNF-alpha was found to increase during 12 h fol
lowing hepatectomy. The maximum of sphingomyelinase activity and accumulati
on of sphingosine preceed the maximum of DNA synthesis. Sphingosine is know
n to inhibit protein kinase C. On the other hand, it stimulates the metabol
ism of phosphatidylinositol, thus causing accumulation of diacylglycerol an
d inositol-1,4,5-triphosphate, which in turn activate protein kinase C. Hen
ce, the release of TNF-a in regenerating liver may modulate DNA synthesis t
hrough the accumulation of sphingosine which is involved in regulation of p
rotein kinase C activity and of phosphatidylinositol turnover.