Bioactive Ceramides in Health and Disease by Johnny Stiban

Author:Johnny Stiban
Language: eng
Format: epub
ISBN: 9783030211622
Publisher: Springer International Publishing

Formation of ceramides-enriched gel phase domains has been observed in simple binary mixtures with fluid POPC (Holopainen et al. 2000a, b; Hsueh et al. 2002; Carrer et al. 2006; Silva et al. 2006; Castro et al. 2007; Pinto et al. 2011), but also with fluid DOPC (Ira and Johnston 2008; Slotte et al. 2017; Al Sazzad et al. 2019). In binary mixtures of C16-ceramide/DOPC, ceramide is able to segregate into ceramide-enriched domains at concentrations above 10 mol% (Al Sazzad et al. 2017). The authors further showed that ceramide gel phase was favored in mixtures with POPC when compared with DOPC for the same ceramide concentration (Al Sazzad et al. 2017, 2019). Molecular dynamic (MD) simulation studies have provided additional clues on the effects of ceramides in phospholipid bilayers. For example, MD simulations performed with different concentrations of C16-ceramide in a DMPC and POPC bilayer further confirmed the ability of ceramides to increase the order of phospholipid bilayers (Dutagaci et al. 2014; Wang and Klauda 2017), as previously shown in experimental studies (Hsueh et al. 2002; Carrer et al. 2006).

Overall, it is consensual that ceramides change the order of fluid phospholipids and drive gel-fluid phase separation in these membranes. However, this effect is not restricted to fluid membranes, and evidence shows that ceramides are also able to affect the properties and lateral organization of gel phase membranes, including in mixtures with DPPC (Massey 2001), DMPC (Holopainen et al. 2000a, b) and DEPE (Jesús et al. 2005). Ceramide and phospholipid gel phase immiscibility was explained by the unfavorable dipolar matching of the lipids (Carrer and Maggio 1999; Carrer et al. 2006). Gel-gel and gel-fluid phase separation was also observed for binary mixtures of ceramides with the sphingolipid SM, depending on the molar ratio between these lipids (Miyaji et al. 2005; Sot et al. 2006; Staneva et al. 2009; Artetxe et al. 2013; Jiménez-Rojo et al. 2014).

Ceramides can be formed by hydrolysis of SM at the PM in response to stress stimuli (Tepper et al. 2000; Kolesnick 2002; Dumitru et al. 2007; Boslem et al. 2012). Therefore, studies that address the interplay between these two lipids are very relevant. Most of the studies so far performed showed that ceramides and SM domains can stabilize each other, and that ceramide’s NH group is extremely important in the stabilization of both gel phases (Maula et al. 2011). Leung et al. (2012) confirmed that ceramide and SM mix well in liquid crystalline state as well as in the gel state for high concentrations of C16-ceramide, thus confirming that C16-ceramide stabilizes C16-SM gel. The extent of ceramides/SM miscibility in the gel and the fluid phase is also dependent on the structure of these lipids. Longer chain ceramides (C16 – C24:1) induced heterogeneities in the membrane corresponding to gel domains of both lipids. The heterogeneities caused by C24:1-ceramide are even more complex due to the interdigitation ability of both ceramide and SM (Jiménez-Rojo et al. 2014). It is suggested that the favorable interactions between ceramides and SM might

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