Sphingomyelin and cholesterol play an important role in stabilising the pla
sma membranes architecture and in many physiological process such as cell g
rowth and differentiation. Degradation of sphingomyelin by exogenous sphing
omyelinase induces a decrease of cholesterol due either to an increase of e
sterification or to a reduced biosynthesis. Variations of sphingomyelin due
to the presence of a neutral-sphingomyelinase and of sphingomyelin-synthas
e have been recently shown in rat liver nuclear membranes. The aim of this
research is to study the relation between sphingomyelin and cholesterol in
the nuclear membranes following sphingomyelinase activation and during cell
proliferation. The nuclear membranes, isolated from liver nuclei, were ana
lysed for their content in protein, nucleic acids, and lipids (sphingomyeli
n and cholesterol) before and after sphingomyelinase activation and during
hepatic regeneration. The activities of nuclear membrane SM-syntase and sph
ingomyelinase were also determined, The results confirmed that also in the
nuclear membranes sphingomyelinase, especially exogenous, causes a strong d
ecrease in cholesterol. The increase observed of sphingomyelin during the f
irst 18 h after hepatectomy followed by a decrease at 24 h, due to the diff
erent activity of the enzymes, is accompanied by similar behaviour of chole
sterol. This confirms the effect of neutral-sphingomyelinase on cholesterol
, due to an increase of esterification process. Changes in cholesterol cont
ent modify the nuclear membranes fluidity and, as consequence, mRNA transpo
rt as previously shown. It can therefore be concluded that the neutral sphi
ngomyelinase, present in the nuclei, may, across this mechanism, regulate t
he cell function. (C) 1999 Academic Press.