Role of acidic sphingomyelinase in Fas/CD95-mediated cell death Journal Article


Authors: Lin, T.; Genestier, L.; Pinkoski, M. J.; Castro, A.; Nicholas, S.; Mogil, R.; Paris, F.; Fuks, Z.; Schuchman, E. H.; Kolesnick, R. N.; Green, D. R.
Article Title: Role of acidic sphingomyelinase in Fas/CD95-mediated cell death
Abstract: Engagement of the Fas receptor has been reported to induce ceramide generation via activation of acidic sphingomyelinase (aSMase). However, the role of aSMase in Fas-mediated cell death is controversial. Using genetically engineered mice deficient in the aSMase gene (aSMase(-/-)), we found that thymocytes, concanavalin A-activated T cells, and lipopolysaccharide- activated B cells derived from both aSMase(-/-) and aSMase(+/+) mice were equally sensitive to Fas-mediated cell death, triggered by either anti-Fas antibody or Fas ligand in vitro. Similarly, activation-induced apoptosis of T lymphocytes was unaffected by the status of aSMase, and aSMase(-/-) mice failed to show immunological symptoms seen in animals with defects in Fas function. In vivo, intravenous injection of 3 μg/25 g mouse body weight of anti-Fas Jo2 antibody into aSMase(-/-) mice failed to affect hepatocyte apoptosis or mortality, whereas massive hepatocyte apoptosis and animal death occurred in wild type littermates. Animals heterozygous for aSMase deficiency were also significantly protected. Susceptibility of aSMase(-/-) mice to anti-Fas antibody was demonstrated with higher antibody doses (≥4 μg/25 g mouse). These data indicate a role for aSMase in Fas-mediated cell death in some but not all tissues.
Keywords: signal transduction; survival analysis; nonhuman; t lymphocyte; animal cell; mouse; animals; mice; mice, knockout; cell death; apoptosis; spleen; fas antigen; b lymphocyte; animalia; liver; thymus gland; membrane glycoproteins; homozygote; lipopolysaccharide; fas ligand protein; receptor; antibodies; thymocyte; ceramides; sphingomyelin phosphodiesterase; antigens, cd95; concanavalin a; priority journal; article
Journal Title: Journal of Biological Chemistry
Volume: 275
Issue: 12
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2000-03-24
Start Page: 8657
End Page: 8663
Language: English
DOI: 10.1074/jbc.275.12.8657
PUBMED: 10722706
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Zvi Fuks
    393 Fuks
  2. Francois Paris
    19 Paris
  3. Richard N Kolesnick
    264 Kolesnick