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Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis.
Open accessAbstract
Recent investigations provided evidence that the sphingomyelin signal transduction pathway mediates apoptosis for tumor necrosis factor alpha (TNF-alpha) in several hematopoietic and nonhematopoietic cells. In this pathway, TNF-receptor interaction initiates sphingomyelin hydrolysis to ceramide by a sphingomyelinase. Ceramide acts as a second messenger stimulating a ceramide-activated serine/threonine protein kinase. The present studies show that ionizing radiation, like TNF, induces rapid sphingomyelin hydrolysis to ceramide and apoptosis in bovine aortic endothelial cells. Elevation of ceramide with exogenous ceramide analogues was sufficient for induction of apoptosis. Protein kinase C activation blocked both radiation-induced sphingomyelin hydrolysis and apoptosis, and apoptosis was restored by ceramide analogues added exogenously. Ionizing radiation acted directly on membrane preparations devoid of nuclei, stimulating sphingomyelin hydrolysis enzymatically through a neutral sphingomyelinase. These studies provide the first conclusive evidence that apoptotic signaling can be generated by interaction of ionizing radiation with cellular membranes and suggest an alternative to the hypothesis that direct DNA damage mediates radiation-induced cell kill.
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Cited by
Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis
Verheij, M., Bose, R., Hua Lin, X., Yao, B., Jarvis, W. D., Grant, S., Birrer, M. J., Szabo, E., Zon, L. I., Kyriakis, J. M., et al. (1996) · Nature · doi:10.1038/380075a0 · Cited by 1,767
Self-citationZamzami, N., Marchetti, P., Castedo, M., Decaudin, D., Macho, A., Hirsch, T., Susin, S. A., Petit, P. X., Mignotte, B., & Kroemer, G. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.2.367 · Cited by 1,567
The sphingolipid salvage pathway in ceramide metabolism and signaling
Kitatani, K., Idkowiak-Baldys, J., & Hannun, Y. A. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2007.12.006 · Cited by 632
Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins
Perona, R., Montaner, S., Saniger, L., Sánchez-Pérez, I., Bravo, R., & Lacal, J. C. (1997) · Genes & Development · doi:10.1101/gad.11.4.463 · Cited by 519
Hematologic consequences of exposure to ionizing radiation
Dainiak, N. (2002) · Experimental Hematology · doi:10.1016/s0301-472x(02)00802-0 · Cited by 362
Metadata
- Authors
- Haimovitz-Friedman, A., Kan, C. C., Ehleiter, D., Persaud, R. S., McLoughlin, M., Fuks, Z., & Kolesnick, R. N.
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1994-08-01
- Volume
- 180
- Issue
- 2
- Pages
- 525-535
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2049108649
- Cited by
- 905
- References
- 0
- FWCI
- 17.77
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Haimovitz-Friedman, A., Kan, C. C., Ehleiter, D., Persaud, R. S., McLoughlin, M., Fuks, Z., & Kolesnick, R. N. (1994). Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. The Journal of experimental medicine. https://doi.org/10.1084/jem.180.2.525
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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