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 localized in the inner nuclear membrane are considered platforms for active chromatin anchoring. Stimuli such as surgery, vitamin D, or glucocorticoid drugs influence their gene expression, DNA duplication, and RNA synthesis. In this study, we used ultrafast liquid chromatography-tandem mass spectrometry to identify sphingomyelin (SM) species coupled with immunoblot analysis to comprehensively map differences in nuclear lipid microdomains (NLMs) purified from hepatocytes and hepatoma cells. We showed that NLMs lost saturated very-long-chain fatty acid (FA; C24:0) SM in cancer cells and became enriched in long-chain FA (C16:0) SM. We also found that signaling proteins, such as STAT3, Raf1, and PKCζ, were increased and vitamin D receptor was reduced in cancer cells. Because 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 SM, C24:0 SM, and cholesterol. Our results led us to hypothesize that the enrichment of C16:0 SM could determine enhanced dynamic properties of NLMs in cancer cells with an increased shuttling of protein signaling molecules.