Cellular electrophile damage by 2-chlorohexadecanal in cardiomyocytes

Background Myeloperoxidase (MPO) activity increases in myocardial infarction due to neutrophil infiltration. MPO together with H2O2 and Cl- leads to the formation of HOCl, which induces plasmalogen modification. HOCl attacks the vinylether bond of plasmalogens inducing formation of alpha-chlorofatty aldehydes, like 2-chlorohexadecanal (2-ClHDA). 2-ClHDA impacts protein function by covalent modification, triggering cytotoxic responses. Methods To study 2-ClHDA-mediated protein modification in cardiomyocytes, click-chemistry with proteomic approaches was used. Therefore, an alkyne containing bioortholog of 2-ClHDA, 2-chlorohexadec-15-yn-1-al (2-ClHDyA), was synthesized. Protein lysates of 2-ClHDyA-modified cardiomyocytes were clicked with tetramethylrhodamine (TAMRA) azide and separated by 2-DE. TAMRA-positive spots were trypsinized and identified by LC-MS/MS. Results During these analyses 51 2-ClHDyA-modified proteins were identified. Those proteins were mainly attributed to cellular processes involved in stress response, the cytoskeleton, and enzymes responsible for energy metabolism. These results suggest that cellular damage following myocardial infarction could be caused by impaired protein function due to modification by 2-ClHDA.