The sphingolipid degradation product trans-2-hexadecenal forms adducts with DNA

Pramod Upadhyaya, Ashok Kumar, Hoe Sup Byun, Robert Bittman, Julie D. Saba, Stephen S. Hecht

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Sphingosine 1-phosphate, a bioactive signaling molecule with diverse cellular functions, is irreversibly degraded by the endoplasmic reticulum enzyme sphingosine 1-phosphate lyase, generating trans-2-hexadecenal and phosphoethanolamine. We recently demonstrated that trans-2-hexadecenal causes cytoskeletal reorganization, detachment, and apoptosis in multiple cell types via a JNK-dependent pathway. These findings and the known chemistry of related α,β-unsaturated aldehydes raise the possibility that trans-2-hexadecenal may interact with additional cellular components. In this study, we show that it reacts readily with deoxyguanosine and DNA to produce the diastereomeric cyclic 1,. N 2-deoxyguanosine adducts 3-(2-deoxy-β-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8. R-hydroxy-6. R-tridecylpyrimido[1,2-a]purine-10(3. H)one and 3-(2-deoxy-β-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8. S-hydroxy-6. S-tridecylpyrimido[1,2-a]purine-10(3. H)one. Thus, our findings suggest that trans-2-hexadecenal produced endogenously by sphingosine 1-phosphate lyase can react directly with DNA forming aldehyde-derived DNA adducts with potentially mutagenic consequences.

Original languageEnglish (US)
Pages (from-to)18-21
Number of pages4
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Jul 20 2012


  • 1,N -propanodeoxyguanosine adducts
  • DNA adducts
  • Sphingosine 1-phosphate
  • Sphingosine 1-phosphate lyase
  • Trans-2-Hexadecenal

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