https://www.ncbi.nlm.nih.gov/pubmed/29354030
Eipä näytä olleenkaan mikään killtti aldehydi, joka vain yksinekrtaisesti oksidoituu edelleen hiilidioksidiksi ja vedeksi.
Biochem Biophys Res Commun. 2012 Jul 20;424(1):18-21. doi: 10.1016/j.bbrc.2012.06.012. Epub 2012 Jun 19.
The sphingolipid degradation product trans-2-hexadecenal forms adducts with DNA.
Abstract
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-8R-hydroxy-6R-tridecylpyrimido[1,2-a]purine-10(3H)one
and
3-(2-deoxy-β-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8S-hydroxy-6S-tridecylpyrimido[1,2-a]purine-10(3H)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.
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-8R-hydroxy-6R-tridecylpyrimido[1,2-a]purine-10(3H)one
and
3-(2-deoxy-β-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8S-hydroxy-6S-tridecylpyrimido[1,2-a]purine-10(3H)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.
- PMID:
- 22727907
- PMCID:
- PMC3402648
- DOI:
- 10.1016/j.bbrc.2012.06.012
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