Covalent modification of DNA by α, β-unsaturated aldehydes derived from lipid peroxidation: Recent progress and challenges

Abstract

Oxidative stress-induced lipid peroxidation (LPO) has been associated with human physiology and pathophysiology. LPO generates an array of oxidation products and among them reactive lipid aldehydes have received intensive research attentions due to their roles in modulating functions of biomolecules through covalent modification. Thus, covalent modification of DNA by these reactive lipid electrophiles has been postulated to be partially responsible for the biological roles of LPO. In this review, we summarized recent progress and challenges in studying the roles of covalent modification of DNA including nuclear and mitochondrial DNA by reactive lipid metabolites from LPO. We focused on the novel mechanistic insights into generation of lipid aldehydes from cellular membranes especially mitochondria through LPO. Recent advances in the technological front using mass spectrometry have also been highlighted in the settings of studying DNA damage caused by LPO and its biological relevance.

Keywords::

• lipid peroxidation
• free radicals
• lipid electrophiles
• DNA modification
• 4-HNE
• mass spectrometry
• adductomics
• mitochondria
• reactive oxygen species

Acknowledgements

This work is supported by grants from the National Natural Science Foundation of China (31170809, 31470831, and 91439103), the National Key Basic Research Program of China (973 Program, #2012CB524905), the Ministry of Science and Technology of China (2012BAK01B00), and the Hundred Talents Program from CAS (2012OHTP07). H.Y. is an Associate Fellow at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine at Nanjing Medical University.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.