Stabilization of sphingomyelin interactions by interfacial hydroxyls — A study of phytosphingomyelin properties

Abstract

D-ribo-phytosphingosines are biologically significant long-chain bases present in various sphingolipids from yeasts, fungi, plants and mammals. In this study we prepared phytopalmitoylsphingomyelin (phytoPSM) analogs based on the D-ribo-phytosphingosine base. The N-linked acyl chains were either 16:0, 2OH(R)16:0 (natural isomer), or 2OH(S)16:0. The gel-phase of phytoPSM was more stable than that of PSM (T(m) 48.6°C and 41.0°C, respectively). The gel-liquid crystalline phase transition enthalpies were 9.1±0.4 and 6.1±0.3kcal/mol for phytoPSM and PSM, respectively. An N-linked 2OH(R)16:0 in phytoPSM destabilized the gel phase relative to phytoPSM (by ~+6°C, based on DPH anisotropy measurements), whereas 2OH(S)16:0 in phytoPSM stabilized it (by ~-6°C). All phytoPSM analogs formed sterol-enriched ordered domains in a fluid ternary bilayer, and those containing phytoPSM or 2OH(S)phytoPSM were more thermostable than the domains containing 2OH(R)phytoPSM or PSM. The affinity of cholestatrienol for POPC bilayers containing 20mol% phytoPSM was higher than for comparable bilayers with an equal amount of PSM. The 2-hydroxylated acyl chains in phytoPSM did not markedly alter sterol affinity. We conclude that phytoPSM is a more ordered sphingolipid than PSM, and is fully capable of interacting with cholesterol.

Mammalian sphingoid bases: Biophysical, physiological and pathological properties

“…However, extrapolation of the biophysical behavior should be made with caution, since the Nacyl chain of SLs strongly influences their biophysical behavior. Nonetheless, it should be stressed that the additional OH group present in the sphingoid backbone seems to be responsible for a higher gel-to-fluid transition temperature of these phytoSLs compared to the SO-based SLs, and higher ability to increase membrane order [197][198][199][200], likely due to stronger network of hydrogen bonds and/or interactions between the polar head groups [198,201]. It can therefore be hypothesized that these stronger interactions are related to the protective effect that PhytoSO-based SLs have in skin, where they are highly abundant [197].…”

“…It can therefore be hypothesized that these stronger interactions are related to the protective effect that PhytoSO-based SLs have in skin, where they are highly abundant [197]. Also noteworthy, is the altered affinity of sterols for membranes containing phytoSphingomyelin compared to SM [200], suggesting that these lipids might influence the organization and properties of the lipid raft domains, and thus raft-dependent signaling events [107]. For example, PhytoSO/PhytoSLenriched ordered domains in biological membranes might be involved in the activation of apoptotic signaling cascades through specific membrane death receptors, which could account for the observed apoptotic effects described for PhytoSO in different cell types.…”

Cholesterol stimulates and ceramide inhibits Sticholysin II-induced pore formation in complex bilayer membranes

“…Multilamellar vesicles were prepared by bath sonication, as described previously [25]. The final lipid concentration was 50 μM and tPa-SM was included at 1 mol%.…”

Influence of Hydroxylation, Chain Length, and Chain Unsaturation on Bilayer Properties of Ceramides

“…In general, SMs and ceramides containing a phytosphingosine backbone display higher gel-to-fluid transition temperatures (as pure components) than analogous sphingolipids with a sphingosine backbone (47,73). For example, C18phyto-cer melts at 110 C (48), whereas C18-cer melts at 91-93 C (9,45).…”

“…1), indicating that in a binary mixture of an a-hydroxylated ceramide and a nonhydroxylated SM, the stabilization of intermolecular interactions by the a-hydroxylation was no longer apparent. Interestingly, both in phytoSM and phytoceramide, introduction of an a-hydroxylation causes a clear reduction in the T m and destabilization of chain interactions (47,48,73), possibly due to weakening of the amide H-bonding ( 47) together with suggested sterical hindrance for acyl chain packing ( 48) induced by the a-hydroxylation. These observations indicate that specific physical properties mediated by a structural detail, such as the a-hydroxylation-induced stabilization of the interlipid interactions of sphingolipids with sphingosine backbone, do not necessarily become transferred as such into other, closely related sphingolipid species, or into mixtures of several sphingolipid species.…”