一个新的鞘脂亚类的发现,(1-脱氧)鞘脂,缺少1-羟基,在过去的十年中引起了相当大的关注,主要是由于他们参与了疾病。它们的物理化学性质与经典(或1-羟基)鞘脂不同,并且在细胞中积累时毒性更大,诱导神经变性和其他功能障碍。(1-脱氧)神经酰胺,(1-脱氧)二氢神经酰胺,和(1-脱氧甲基)二氢神经酰胺,后两者含有饱和鞘氨醇链,在这项工作中已经使用差示扫描量热法进行了研究,共聚焦荧光和原子力显微镜,评估它们在由三种或四种脂质混合物组成的双层中的行为。与经典神经酰胺(Cer)相比,aC16:0(1-脱氧)Cer在C16:0鞘磷脂/胆固醇/XCer的混合物中显示出较低的混溶性,其中XCer是任何(1-脱氧)神经酰胺,导致液体有序相和凝胶相共存。后者类似,在热致行为和纳米机械阻力方面,C16:0鞘磷脂/胆固醇/C16:0Cer混合物的凝胶相[Busto等人。,生物群落。J.2014,106,621-630]。在纳米机械阻力方面,研究中的各种C16:0XCer之间存在差异,双层厚度和双层形貌。当在更流体的环境(基于C24:1SM的双层)中检查时,分离的凝胶相仍然存在。可能与这种横向分离有关,XCer保持膜渗透的能力,但它们的效果明显低于经典神经酰胺。此外,C24:1XCer显示出比它们的C16:0对应物显著更低的膜渗透能力。上述数据可能与某些鞘脂相关疾病的发病机制有关。包括某些神经病,糖尿病,和糖原贮积病。
The discovery of a novel sphingolipid subclass, the (1-deoxy)sphingolipids, which lack the 1-hydroxy group, attracted considerable attention in the last decade, mainly due to their involvement in disease. They differed in their physico-chemical properties from the canonical (or 1-hydroxy) sphingolipids and they were more toxic when accumulated in cells, inducing neurodegeneration and other dysfunctions. (1-Deoxy)ceramides, (1-deoxy)dihydroceramides, and (1- deoxymethyl)dihydroceramides, the latter two containing a saturated sphingoid chain, have been studied in this work using differential scanning calorimetry, confocal fluorescence and atomic force microscopy, to evaluate their behavior in bilayers composed of mixtures of three or four lipids. When compared to canonical ceramides (Cer), a C16:0 (1-deoxy)Cer shows a lower miscibility in mixtures of the kind C16:0 sphingomyelin/cholesterol/XCer, where XCer is any (1-deoxy)ceramide, giving rise to the coexistence of a liquid-ordered phase and a gel phase. The latter resembles, in terms of thermotropic behavior and nanomechanical resistance, the gel phase of the C16:0 sphingomyelin/cholesterol/C16:0 Cer mixture [Busto et al., Biophys. J. 2014, 106, 621-630]. Differences are seen between the various C16:0 XCer under study in terms of nanomechanical resistance, bilayer thickness and bilayer topography. When examined in a more fluid environment (bilayers based on C24:1 SM), segregated gel phases are still present. Probably related to such lateral separation, XCer preserve the capacity for membrane permeation, but their effects are significantly lower than those of canonical ceramides. Moreover, C24:1 XCer show significantly lower membrane permeation capacity than their C16:0 counterparts. The above data may be relevant in the pathogenesis of certain sphingolipid-related diseases, including certain neuropathies, diabetes, and glycogen storage diseases.