CerS2 ko in vivo reduces pro-inflammatory ceramides and improves doxorubicin mediated cardiotoxicity

Abstract Background Ceramides and their role in various signaling pathways are believed to regulate distinct cellular effects. Accumulation of ceramides seems to be associated with an inflammatory phenotype negatively affecting cardiomyocyte vitality and mitochondrial homeostasis. Aim The purpose of our study is to identify underlying ceramide signaling pathways and characterize downstream effects on cell vitality of cardiomyocytes. Methods A CerS2 ko mouse model was generated and the animals were treated with 7 cumulative doses of 3 mg/kg BW Doxorubicin (Dox). Subsequently, hearts were extracted and analyzed, including mRNA (qPCR) and protein expression (WB) and ceramide level (mass spectrometry). Results The CerS2 ko was stable and Dox injection did not increase CerS2 protein expression. Mass spectrometry revealed an increase of long chain ceramides (C≤20) with the highest peak for C18:0 (5.08 ± 0.21, p