Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 275, Issue 12, Pages 8657-8663Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.275.12.8657
Keywords
-
Categories
Funding
- NCI NIH HHS [CA69381, CA42385] Funding Source: Medline
- NIDDK NIH HHS [DK02445] Funding Source: Medline
Ask authors/readers for more resources
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 mu g/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 (greater than or equal to 4 mu g/25 g mouse). These data indicate a role for aSMase in Fas-mediated cell death in some but not all tissues.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available