Abstract
Ceramide (Cer) is involved in the regulation of several cellular processes by mechanisms that depend on Cer-induced changes on membrane biophysical properties. Accumulating evidence shows that Cers with different N-acyl chain composition differentially impact cell physiology, which may in part be due to specific alterations in membrane biophysical properties. We now address how the sphingolipid (SL) N-acyl chain affects membrane properties in cultured human embryonic kidney cells by overexpressing different Cer synthases (CerSs). Our results show an increase in the order of cellular membranes in CerS2-transfected cells caused by the enrichment in very long acyl chain SLs. Formation of Cer upon treatment of cells with bacterial sphingomyelinase promoted sequential changes in the properties of the membranes: after an initial increase in the order of the fluid plasma membrane, reorganization into domains with gel-like properties whose characteristics are dependent on the acyl chain structure of the Cer was observed. Moreover, the extent of alterations of membrane properties correlates with the amount of Cer formed. These data reinforce the significance of Cer-induced changes on membrane biophysical properties as a likely molecular mechanism by which different acyl chain Cers exert their specific biological actions.
Highlights
Ceramide (Cer) is involved in the regulation of several cellular processes by mechanisms that depend on Cer-induced changes on membrane biophysical properties
To evaluate the impact of SL acyl chain composition on membrane biophysical properties, human embryonic kidney (HEK) cells were transfected with CerS2 in order to increase levels of very long acyl chain (VLC)-SLs (C22– C24) (Fig. 1) or with CerS5 to increase levels of C16-SLs [10, 11] (Fig. 1)
Similar to previous results [11], transfection of HEK cells with CerS2 resulted in a significant increase in VLC-SLs (Fig. 1A, B) and a slight increase in unsaturated SLs (Fig. 1C), which was mainly due to elevation in levels of C24:1-SLs
Summary
Ceramide (Cer) is involved in the regulation of several cellular processes by mechanisms that depend on Cer-induced changes on membrane biophysical properties. The extent of alterations of membrane properties correlates with the amount of Cer formed These data reinforce the significance of Cer-induced changes on membrane biophysical properties as a likely molecular mechanism by which different acyl chain Cers exert their specific biological actions.—Pinto, S. Under the influence of several agents (e.g., Fas ligand, TNF-␣, nitric oxide), SM is hydrolyzed by sphingomyelinases (SMases) to generate Cer, driving the formation of Cer-enriched domains, known as Cer platforms [4,5,6,7,8,9] The formation of these platforms has a strong impact on cell biology as the tightly packed Cer molecules induce the clustering of cell death receptors which initiate signaling cascades that lead to cell death [4]. Understanding how membrane biophysical properties are affected upon generation of Cer with specific acyl chains is crucial for understanding the correlation between the cellular roles of Cer and its biophysical properties
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