Chromatin‐associated sphingomyelin: metabolism in relation to cell function

Abstract

After the first histochemical demonstration by Chayen and Gahan of the presence of phospholipids and especially of sphingomyelin in chromatin, this became the object of long debate and of contradictory results. The general conclusion was that the presence of phospholipids may due to contamination during the isolation of chromatin. More recently the existence of a phospholipid chromatin fraction was confirmed by demonstrating that isolated hepatocyte nuclei, labelled by saturated and unsaturated radioiodination method, showed the presence of radioactivity only in the membrane and not in the isolated chromatin. The phospholipid composition showed an enrichment in sphingomyelin which increased during hepatocyte maturation or erythroleukemic cell differentiation induced by DMSO. A decrease in sphingomyelin was observed at the beginning of the Sphase in regenerating liver or in cultured proliferating cells. These changes were due to the presence of sphingomyelinase and sphingomyelin synthase in the chromatin, the activity of which paralleled the variation in sphingomyelin content. The sphingomyelin was co-localized with RNA as shown by biochemical and electron microscopy methods. Using bromo-uridine it was demonstrated that labelled RNA and sphingomyelin were present in actively transcribing nuclear regions. Isolated nuclear complexes after DNase and RNase digestion contained not only protein, but also RNA and sphingomyelin. After hydrolysis of sphingomyelin the RNAse-resistant RNA becomes RNAse sensitive. It can therefore be concluded that sphingomyelin and the related enzymes are present in the chromatin; sphingomyelin may have a role in RNA transcription protecting RNA by RNAse digestion before its transfer to the cytoplasm.

Adenovirus-mediated overexpression of sphingomyelin synthases 1 and 2 increases the atherogenic potential in mice

“…Many studies indicate that SM synthase is located mainly in the cis -medial Golgi (19)(20)(21) and plasma membranes (22)(23)(24). In addition, SMS activity has been found in chromatin, and chromatin-associated SMS modifies SM content (25)(26)(27). Despite the biological importance of SMS, understanding of the molecular mechanisms of its regulation and its relationship with plasma SM levels is limited by the fact that no successful purification of this protein has been achieved.…”

Nuclear sphingomyelin pathway in serum deprivation‐induced apoptosis of embryonic hippocampal cells

“…As consequence of nuclear SMase activity, a peak of nuclear ceramide was observed 2 h after deprivation followed by a decrease in SM content. In fact the activation of SMase was accompanied by an inhibition of SM-synthase suggesting a reciprocal control between the two enzymes as previously observed in hepatocyte nuclei (Albi and Viola Magni, 2003a). An increase of SMase in the homogenate was observed only 8 h after deprivation, when the number of HN9.10.e cells in the S phase begins to decrease with a corresponding increase of the cells in G 1 .…”

Biophysical analysis of bacterial and viral systems. A shock tube study of bio-aerosols and a correlated AFM/nanosims investigation of vaccinia virus

“…While this data brings into question the fidelity of the 13 C labeling procedure it is interesting to note that a number of studies have indicated that a multitude of phospholipids may be metabolized and associated with nuclear assemblages [68][69][70] .…”

“…In addition, evidence indicates that a variety of phospholipids may act as lipid mediators during nuclear processes such as DNA transcription, splicing and repair 69,70 . The cellular metabolism of lipids, then, may have resulted in the distribution of the 13 C label to an array of viral components during inter-cellular virion assembly.…”