Abstract:
:The sphingomyelin pathway, which is initiated by sphingomyelin hydrolysis to generate the second messenger ceramide, signals apoptosis for tumor necrosis factor alpha, Fas, and ionizing radiation. In the present studies, the anticancer drug daunorubicin also stimulated ceramide elevation and apoptosis in P388 and U937 cells. Cell-permeable analogs of ceramide, but not other lipid second messengers, mimicked daunorubicin in inducing apoptosis. Daunorubicin-stimulated ceramide elevation, however, did not result from sphingomyelin hydrolysis, but rather from de novo synthesis via activation of the enzyme ceramide synthase. An obligatory role for ceramide synthase was defined, since its natural specific inhibitor, fumonisin B1, blocked daunorubicin-induced ceramide elevation and apoptosis. These studies demonstrate that ceramide synthase activity can be regulated in eukaryotes and constitute definitive evidence for a requirement for ceramide elevation in the induction of apoptosis.
journal_name
Celljournal_title
Cellauthors
Bose R,Verheij M,Haimovitz-Friedman A,Scotto K,Fuks Z,Kolesnick Rdoi
10.1016/0092-8674(95)90429-8subject
Has Abstractpub_date
1995-08-11 00:00:00pages
405-14issue
3eissn
0092-8674issn
1097-4172pii
0092-8674(95)90429-8journal_volume
82pub_type
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