Background: Platforms in internuclear membrane are constituted by lipid microdomains with a ratio among cholesterol (CHO), phosphatidylcholine (PC) and sphingomyelin (SM) of about 1:1:1, characteristic of the lipid rafts. Nuclear lipid rafts (NLRs) act as a platform for RNA synthesis. The newly synthesized RNA is protected by SM from RNase action. In liver regeneration, during G1/S transition, SM and DNA content in NLR are very high and are strongly reduced after sphingomyelinase treatment. During the S-phase, stimulation of sphingomyelinase and inhibition of SMSynthase are accompanied by DNA synthesis. Thus, NLR represents an inner nuclear membrane area that acts as an active site of chromatin anchorage thanks to the stabilizing action of SM. Methods: Since NLR-SM regulates cell proliferation, we performed a lipidomic study by comparing NLR purified from hepatocyte and hepatoma nuclei (H35 cells). Ultra Fast Liquid chromatography tandem mass spectrometry (UFLC-MS/MS) was used. Results: Results showed that, in comparison with NLM from normal liver, NLR from H35 cells are enriched in SM and PC saturated fatty acids (SM 16:0, SM 24:0, PC 16:0). Conclusions: This justifies the high content of CHO found in the H35 NLR. The high amount of saturated fatty acids in SM and PC favours the formation of Van der Waals interactions with CHO. H35 NLR is thus highly rigid allowing the attachment of active chromatin and facilitating replication and transcription of DNA. As the nuclear lipid content is influenced by diet, the reduction of the use of saturated fatty acids may slow tumor growth.
A lipidomic study of sphingomyelin localized in lipid rafts from normal liver and hepatoma cells
CATALDI, SAMUELA;CODINI, Michela;BECCARI, Tommaso;ALBI, Elisabetta
2014
Abstract
Background: Platforms in internuclear membrane are constituted by lipid microdomains with a ratio among cholesterol (CHO), phosphatidylcholine (PC) and sphingomyelin (SM) of about 1:1:1, characteristic of the lipid rafts. Nuclear lipid rafts (NLRs) act as a platform for RNA synthesis. The newly synthesized RNA is protected by SM from RNase action. In liver regeneration, during G1/S transition, SM and DNA content in NLR are very high and are strongly reduced after sphingomyelinase treatment. During the S-phase, stimulation of sphingomyelinase and inhibition of SMSynthase are accompanied by DNA synthesis. Thus, NLR represents an inner nuclear membrane area that acts as an active site of chromatin anchorage thanks to the stabilizing action of SM. Methods: Since NLR-SM regulates cell proliferation, we performed a lipidomic study by comparing NLR purified from hepatocyte and hepatoma nuclei (H35 cells). Ultra Fast Liquid chromatography tandem mass spectrometry (UFLC-MS/MS) was used. Results: Results showed that, in comparison with NLM from normal liver, NLR from H35 cells are enriched in SM and PC saturated fatty acids (SM 16:0, SM 24:0, PC 16:0). Conclusions: This justifies the high content of CHO found in the H35 NLR. The high amount of saturated fatty acids in SM and PC favours the formation of Van der Waals interactions with CHO. H35 NLR is thus highly rigid allowing the attachment of active chromatin and facilitating replication and transcription of DNA. As the nuclear lipid content is influenced by diet, the reduction of the use of saturated fatty acids may slow tumor growth.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
