Ceramide synthase mediates daunorubicin-induced apoptosis: An alternative mechanism for generating death signals Journal Article

  


Authors: Bose, R.; Verheij, M.; Haimovitz-Friedman, A.; Scotto, K.; Fuks, Z.; Kolesnick, R.
Article Title: Ceramide synthase mediates daunorubicin-induced apoptosis: An alternative mechanism for generating death signals
Abstract: The sphingomyelin pathway, which is initiated by sphingomyelin hydrolysisto generate the second messenger ceramide, signals apoptosis for tumor necrosis factor α, 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. © 1995.
Keywords: signal transduction; nonhuman; animal cell; mouse; animal; mice; apoptosis; dna; enzyme regulation; regulatory mechanism; tumor necrosis factor alpha; daunorubicin; ionizing radiation; cell line, transformed; arachidonic acid; amidohydrolases; hydrolysis; diacylglycerol; phosphatidic acid; ceramide; sphingosine acyltransferase; second messenger; etiology; fumonisin b1; second messenger systems; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: Cell
Volume: 82
Issue: 3
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 1995-08-11
Start Page: 405
End Page: 414
Language: English
DOI: 10.1016/0092-8674(95)90429-8
PUBMED: 7634330
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0029148660&doi=10.1016%2f0092-8674%2895%2990429-8&partnerID=40&md5=65705eca054bc1743a2dbb6579a23366
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus
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MSK Authors
  1. Kathleen Weihs Scotto
    56 Scotto
  2. Zvi Fuks
    427 Fuks
  3. Adriana Haimovitz-Friedman
    170 Haimovitz-Friedman
  4. Richard N Kolesnick
    299 Kolesnick
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