Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis Journal Article
| Authors: | Haimovitz-Friedman, A.; Kan, C. C.; Ehleiter, D.; Persaud, R. S.; McLoughlin, M.; Fuks, Z.; Kolesnick, R. N. |
| Article Title: | Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis |
| Abstract: | Recent investigations provided evidence that the sphingomyelin signal transduction pathway mediates apoptosis for tumor necrosis factor α(TNF-α) in several hematopoietic and nonhematopoietic ceils. 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 su-cient 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. © 1994, Rockefeller University Press., All rights reserved. |
| Keywords: | signal transduction; nonhuman; animal cell; animal; dna damage; cells, cultured; apoptosis; enzyme activation; radiation injury; cell membrane; hematopoietic stem cells; ionizing radiation; radiation, ionizing; cattle; cell interaction; hydrolysis; cell killing; ceramide; ceramides; dna degradation; cell surface receptor; sphingomyelin phosphodiesterase; dna content; second messenger systems; sphingomyelins; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 180 |
| Issue: | 2 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 1994-08-01 |
| Start Page: | 525 |
| End Page: | 535 |
| Language: | English |
| DOI: | 10.1084/jem.180.2.525 |
| PROVIDER: | scopus |
| PMCID: | PMC2191598 |
| PUBMED: | 8046331 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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