title: 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?
abstract: 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.
authors.affiliation: Laboratory of Nuclear Lipid BioPathology, CRABiON, 06100 Perugia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lazzarini
authors.affiliation: Department of Pharmaceutical Science, University of Perugia, 06123 Perugia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Macchiarulo
authors.affiliation: Laboratory of Nuclear Lipid BioPathology, CRABiON, 06100 Perugia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Floridi
authors.affiliation: Department of Pharmaceutical Science, University of Perugia, 06123 Perugia, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Coletti
authors.affiliation: Department of Pharmaceutical Science, University of Perugia, 06123 Perugia, Italy.
authors.forename: Samuela
authors.initials: S
authors.lastname: Cataldi
authors.affiliation: Department of Pharmaceutical Science, University of Perugia, 06123 Perugia, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Codini
authors.affiliation: Laboratory of Nuclear Lipid BioPathology, CRABiON, 06100 Perugia, Italy.
authors.forename: Remo
authors.initials: R
authors.lastname: Lazzarini
authors.affiliation: Laboratory of Nuclear Lipid BioPathology, CRABiON, 06100 Perugia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bartoccini
authors.affiliation: Laboratory of Nuclear Lipid BioPathology, CRABiON, 06100 Perugia, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cascianelli
authors.affiliation: Department of Clinical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Ambesi-Impiombato
authors.affiliation: Department of Pharmaceutical Science, University of Perugia, 06123 Perugia, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Beccari
authors.affiliation: Department of Clinical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Curcio
authors.affiliation: Laboratory of Nuclear Lipid BioPathology, CRABiON, 06100 Perugia, Italy elisabetta.albi@yahoo.com.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Albi
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D047908:Intracellular Signaling Peptides and Proteins; D018167:Receptors, Calcitriol; D013107:Sphingolipids; D013109:Sphingomyelins; D002784:Cholesterol