Cycloheximide in sublethal doses caused apoptosis in liver cells in vi
vo, inducing c-myc, c-fos, c-jun and p53 genes and accumulation of sph
ingosine, a toxic product of the sphingomyelin cycle, These data suppo
rt the hypothesis that continuous synthesis of labile protective prote
ins is required to restrain apoptosis in liver; sphingosine might be i
mportant in mediating cycloheximide-induced apoptosis as an endogenous
modulator of protein kinase C activity. (C) 1997 Federation of Europe
an Biochemical Societies.