Radiation and ceramide-induced apoptosis Journal Article
| Authors: | Kolesnick, R.; Fuks, Z. |
| Article Title: | Radiation and ceramide-induced apoptosis |
| Abstract: | Ceramide is a sphingolipid that acts as a second messenger in ubiquitous, evolutionarily conserved, signaling systems. Emerging data suggest that radiation acts directly on the plasma membrane of several cell types, activating acid sphingomyelinase, which generates ceramide by enzymatic hydrolysis of sphingomyelin. Ceramide then acts as a second messenger in initiating an apoptotic response via the mitochondrial system. Radiation-induced DNA damage can also initiate ceramide generation by activation of mitochondrial ceramide synthase and de novo synthesis of ceramide. In some cells and tissues, BAX is activated downstream of ceramide, regulating commitment to the apoptotic process via release of mitochondrial cytochrome c. Genetic and pharmacologic studies in vivo showed that radiation targets the acid sphingomyelinase apoptotic system of microvascular endothelial cells in the lungs, intestines and brain, as well as in oocytes, to initiate the pathogenesis of tissue damage. Regulated ceramide metabolism may produce metabolites, such as sphingosine 1-phosphate, shown to signal antiapoptosis, thus controlling the intensity of the apoptotic response and constituting a mechanism for radiation sensitivity or resistance. An improved understanding of this signaling system may offer new opportunities for the modulation of radiation effects in the treatment of cancer. |
| Keywords: | signal transduction; unclassified drug; pathogenesis; review; nonhuman; animal; animals; cell death; dna damage; apoptosis; radiation; enzyme activation; drug effect; enzyme inhibitor; radiation exposure; radiation response; radiosensitivity; ras protein; microvasculature; mitochondrial protein; tissue injury; lipid metabolism; mitochondrion; lipogenesis; rac protein; ceramide; ceramides; protein kinase c inhibitor; sphingomyelin phosphodiesterase; lipid analysis; sphingosine acyltransferase; sphingomyelin; second messenger; cytochrome c; protein bax; sphingosine 1 phosphate; sphingomyelinase; second messenger systems; humans; human; priority journal; n oleoylethanolamine; recombinant tumor necrosis factor alpha |
| Journal Title: | Oncogene |
| Volume: | 22 |
| Issue: | 37 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2003-09-01 |
| Start Page: | 5897 |
| End Page: | 5906 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1206702 |
| PUBMED: | 12947396 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 25 September 2014 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work