Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis Journal Article

  


Authors: Santana, P.; Peña, L. A.; Haimovitz-Friedman, A.; Martin, S.; Green, D.; McLoughlin, M.; Cordon-Cardo, C.; Schuchman, E. H.; Fuks, Z.; Kolesnick, R.
Article Title: Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis
Abstract: Stress is believed to activate sphingomyelinase to generate ceramide, which serves as a second messenger in initiating the apoptotic response. Conclusive evidence for this paradigm, however, is lacking. In the present study, we used a genetic approach to address this issue directly. We show that lymphoblasts from Niemann-Pick patients, which have an inherited deficiency of acid sphingomyelinase activity, fail to respond to ionizing radiation with ceramide generation and apoptosis. These abnormalities are reversible upon restoration of acid sphingomyelinase activity by retroviral transfer of human acid sphingomyelinase cDNA. Acid sphingomyelinase knockout mice also expressed defects in radiation-induced ceramide generation and apoptosis in vivo. Comparison with p53 knockout mice revealed that acid sphingomyelinase-mediated apoptosis and p53-mediated apoptosis are likely distinct and independent. These genetic models provide definitive evidence for the involvement of acid sphingomyelinase in one form of stress-induced apoptosis.
Keywords: human tissue; human cell; nonhuman; animal cell; mouse; animal tissue; apoptosis; enzyme activation; gene expression regulation; diagnosis; transactivation; ionizing radiation; radiation hazard; complementary dna; ceramide; sphingomyelin phosphodiesterase; second messenger; niemann pick disease; lymphoblast; human; priority journal; article
Journal Title: Cell
Volume: 86
Issue: 2
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 1996-07-26
Start Page: 189
End Page: 199
Language: English
DOI: 10.1016/s0092-8674(00)80091-4
PUBMED: 8706124
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-16044364385&doi=10.1016%2fS0092-8674%2800%2980091-4&partnerID=40&md5=6f5db65a32f0c9d6ded50eab2ca76b8f
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
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MSK Authors
  1. Zvi Fuks
    427 Fuks
  2. Carlos Cordon-Cardo
    612 Cordon-Cardo
  3. Adriana Haimovitz-Friedman
    170 Haimovitz-Friedman
  4. Richard N Kolesnick
    299 Kolesnick
  5. Louis A Pena
    7 Pena
  6. Maureen McLoughlin
    17 McLoughlin
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