The Notch ligand, Delta-1, reduces TNF-α-induced growth suppression and apoptosis by decreasing activation of caspases in U937 cells

  • Authors:
    • Mai Murata-Ohsawa
    • Shuji Tohda
    • Hanae Kogoshi
    • Nobuo Nara
  • View Affiliations

  • Published online on: November 1, 2004     https://doi.org/10.3892/ijmm.14.5.861
  • Pages: 861-866
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The Notch signaling pathway plays an important role in the regulation of self-renewal and differentiation of hematopoietic progenitors. Tumor necrosis factor (TNF)-α induces apoptosis through activation of caspase pathway. A monoblastic leukemia cell line, U937, undergoes apoptosis following stimulation with TNF-α. We found that Notch activation induced by a recombinant Notch ligand, Delta-1, reduced the TNF-α-induced growth suppression and apoptosis in U937 cells. As the molecular mechanism involved, we showed Delta-1 stimulation partially suppressed the sequential activation of caspase-8, caspase-3, and, PARP induced by TNF-α. The TNF-α-induced activation of c-Jun N-terminal kinase (JNK), p38, and NF-κB was not affected by Delta-1 stimulation. The cells needed to be exposed to Delta-1 prior to TNF-α stimulation to reduce the suppressive effect of TNF-α. Therefore, we thought that Delta-1 stimulation might reduce the expression of TNF-receptor (R) 1 and proteins to modulate the activation of caspases such as FLIP and XIAP. However, Delta-1 stimulation did not affect their expression. The precise mechanism by which Notch signaling suppresses caspase activation has yet to be determined. This is the first report to show the relationship between Notch activation and TNF-R1 signaling. The findings suggest possible mechanisms by which Notch activation supports cell survival.

Related Articles

Journal Cover

November 2004
Volume 14 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Murata-Ohsawa M, Tohda S, Kogoshi H and Nara N: The Notch ligand, Delta-1, reduces TNF-α-induced growth suppression and apoptosis by decreasing activation of caspases in U937 cells. Int J Mol Med 14: 861-866, 2004
APA
Murata-Ohsawa, M., Tohda, S., Kogoshi, H., & Nara, N. (2004). The Notch ligand, Delta-1, reduces TNF-α-induced growth suppression and apoptosis by decreasing activation of caspases in U937 cells. International Journal of Molecular Medicine, 14, 861-866. https://doi.org/10.3892/ijmm.14.5.861
MLA
Murata-Ohsawa, M., Tohda, S., Kogoshi, H., Nara, N."The Notch ligand, Delta-1, reduces TNF-α-induced growth suppression and apoptosis by decreasing activation of caspases in U937 cells". International Journal of Molecular Medicine 14.5 (2004): 861-866.
Chicago
Murata-Ohsawa, M., Tohda, S., Kogoshi, H., Nara, N."The Notch ligand, Delta-1, reduces TNF-α-induced growth suppression and apoptosis by decreasing activation of caspases in U937 cells". International Journal of Molecular Medicine 14, no. 5 (2004): 861-866. https://doi.org/10.3892/ijmm.14.5.861