Aslan Mutay, Kıraç Ebru, Kaya Sabriye, Özcan Filiz, Salim Ozan, Küpesiz Osman Alphan
Department of Medical Biochemistry, Akdeniz University Medical School, 07070, Antalya, Turkey.
Department of Hematology, Akdeniz University, Faculty of Medicine, 07070, Antalya, Turkey.
Lipids. 2018 Mar;53(3):313-322. doi: 10.1002/lipd.12027. Epub 2018 Apr 16.
Limited data are available on the serum levels of different sphingomyelin (CerPCho) and ceramide (CER) species in sickle-cell disease (SCD). This study was aimed at identifying the levels of C16-C24 CerPCho and C16-C24 CER in serum obtained from SCD patients and controls. Circulating levels of neutral sphingomyelinase (N-SMase) activity, ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P) were also determined. Blood was collected from 35 hemoglobin (Hb)A volunteers and 45 homozygous HbSS patients. Serum levels of C16-C24 CerPCho and C16-C24 CER were determined by an optimized multiple reaction monitoring (MRM) method using ultrafast liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Serum activity of N-SMase was assayed by standard kit methods, and C1P and S1P levels were determined by enzyme-linked immunosorbent assay. A significant decrease was observed in the serum levels of C18-C24 CerPCho in patients with SCD compared to controls. No significant difference was found in C16 CerPCho levels between the two groups. Very-long-chain C22-C24 CER were significantly decreased in SCD, while long-chain C16-C20 CER levels showed no significant difference between SCD patients and controls. Significant positive correlation was found between the serum total cholesterol levels and C18-C24 CerPCho and C22-C24 CER in SCD patients. Patients with SCD had significantly elevated serum activity of N-SMase as well as increased circulating levels of C1P and S1P compared to controls. The decrease in serum levels of C18-C24 CerPCho in patients with SCD was accompanied by decreased levels of C22-C24 CER. Future studies are needed to understand the role of decreased CerPCho and CER in the pathophysiology of SCD.
关于镰状细胞病（SCD）患者血清中不同鞘磷脂（神经酰胺磷酰胆碱，CerPCho）和神经酰胺（CER）种类的水平，现有数据有限。本研究旨在确定从SCD患者和对照组获取的血清中C16 - C24 CerPCho和C16 - C24 CER的水平。同时还测定了循环中性鞘磷脂酶（N - SMase）活性、神经酰胺 - 1 - 磷酸（C1P）和鞘氨醇 - 1 - 磷酸（S1P）的水平。采集了35名血红蛋白（Hb）A志愿者和45名纯合HbSS患者的血液。采用超快速液相色谱（UFLC）与串联质谱（MS/MS）联用的优化多反应监测（MRM）方法测定血清中C16 - C24 CerPCho和C16 - C24 CER的水平。通过标准试剂盒方法检测N - SMase的血清活性，采用酶联免疫吸附测定法测定C1P和S1P水平。与对照组相比，SCD患者血清中C18 - C24 CerPCho水平显著降低。两组之间C16 CerPCho水平未发现显著差异。SCD患者中极长链C22 - C24 CER显著降低，而长链C16 - C20 CER水平在SCD患者和对照组之间未显示出显著差异。在SCD患者中，血清总胆固醇水平与C18 - C24 CerPCho和C22 - C24 CER之间存在显著正相关。与对照组相比，SCD患者血清N - SMase活性显著升高，同时C1P和S1P的循环水平也升高。SCD患者血清中C18 - C24 CerPCho水平降低的同时，C22 - C24 CER水平也降低。未来需要进一步研究以了解CerPCho和CER水平降低在SCD病理生理学中的作用。
