Very-long-chain fatty acid sphingomyelin in nuclear lipid microdomains of hepatocytes and hepatoma cells: can the exchange from C24:0 to C16:0 affect signal proteins and vitamin D receptor?

Lipid microdomains localised in inner nuclear membrane are considered platforms for active chromatin anchoring. Stimuli as surgery, vitamin D or glucocorticoid drugs influence there gene expression, DNA duplication and RNA synthesis. Here, we used ultra fast liquid chromatography tandem mass spectrometry to identify sphingomyelin species coupled with immunoblotting analysis to comprehensively map differences in nuclear lipid microdomains purified from hepatocytes and hepatoma cells. We showed that nuclear lipid microdomains lost saturated very long fatty acid (C24:0) sphingomyelin in cancer cells and enriched in long fatty acid (C16:0) sphingomyelin. We also found that signaling proteins, such as STAT3, Raf1, and PKCζ, were increased and Vitamin D receptor was reduced in cancer cells. Since recent researches showed a shift in sphingolipid composition from C24:0 to C16:0 in relation to cell life, we performed a comparative analysis of properties among C16:0 sphingomyelin, C24:0 sphingomyelin and cholesterol. Our results induced to hypothesise that the enrichment of C16:0 sphingomyelin could determine enhanced dynamic properties of nuclear lipid microdomains in cancer cells with an increased shuttling of proteins signaling molecules.