Division of Biological Chemistry, Biocenter, Innsbruck Medical University, 6020 Innsbruck, Austria.
J Lipid Res. 2012 Jul;53(7):1410-6. doi: 10.1194/jlr.D025650. Epub 2012 Apr 16.
The lack of fatty aldehyde dehydrogenase function in Sjögren Larsson Syndrome (SLS) patient cells not only impairs the conversion of fatty aldehydes into their corresponding fatty acid but also has an effect on connected pathways. Alteration of the lipid profile in these cells is thought to be responsible for severe symptoms such as ichtyosis, mental retardation, and spasticity. Here we present a novel approach to examine fatty aldehyde metabolism in a time-dependent manner by measuring pyrene-labeled fatty aldehyde, fatty alcohol, fatty acid, and alkylglycerol in the culture medium of living cells using HPLC separation and fluorescence detection. Our results show that in fibroblasts from SLS patients, fatty aldehyde is not accumulating but is converted readily into fatty alcohol. In control cells, in contrast, exclusively the corresponding fatty acid is formed. SLS patient cells did not display a hypersensitivity toward hexadecanal or hexadecanol, but 3-fold lower concentrations of the fatty alcohol than the corresponding fatty aldehyde were needed to induce toxicity in SLS patient and in control cells.
干燥综合征-口炎性腹泻综合征（SLS）患者细胞中缺乏脂肪醛脱氢酶功能，不仅会损害脂肪醛转化为相应脂肪酸的过程，还会对相关途径产生影响。这些细胞中脂质谱的改变被认为是导致严重症状（如鱼鳞癣、智力迟钝和痉挛）的原因。在这里，我们提出了一种新的方法，通过使用 HPLC 分离和荧光检测，在活细胞的培养基中测量芘标记的脂肪醛、脂肪醇、脂肪酸和烷基甘油，以时间依赖性方式检查脂肪醛代谢。我们的结果表明，在 SLS 患者的成纤维细胞中，脂肪醛不会积累，而是很容易转化为脂肪醇。相比之下，在对照细胞中，仅形成相应的脂肪酸。SLS 患者细胞对十六醛或十六醇没有表现出超敏性，但诱导 SLS 患者和对照细胞毒性所需的脂肪醇浓度比相应的脂肪醛低 3 倍。
