期刊
CLINICA CHIMICA ACTA
卷 542, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.cca.2023.117295
关键词
Peroxisome biogenesis defects; Rhizomelic chondrodysplasia punctata; Plasmalogen
Plasmalogens are glycerophospholipids with important roles in cellular processes, and their deficiency is associated with neurodegenerative diseases and peroxisome biogenesis disorders. A novel LC-MS/MS method was developed to quantify phosphoethanolamine plasmalogens in red blood cells, providing a specific and precise diagnostic tool. This method has the potential to enhance our understanding of disease pathogenesis and monitor therapy.
Plasmalogens are glycerophospholipids characterized by a vinyl-ether bond with a fatty alcohol at the sn-1 position, a polyunsaturated fatty acid at the sn-2 position, and a polar head at the sn-3 position, commonly phosphoethanolamine. Plasmalogens play crucial roles in several cellular processes. Reduced levels have been associated with Alzheimer's and Parkinson's disease progression. Markedly reduced plasmalogens are a classic feature of peroxisome biogenesis disorders (PBD) because plasmalogen synthesis requires functional peroxi-somes. Particularly, severe plasmalogen deficiency is the biochemical hallmark of rhizomelic chondrodysplasia punctata (RCDP). Traditionally, plasmalogens are evaluated in red blood cells (RBCs) by gas-chromatography/ mass-spectrometry (GC-MS), which cannot distinguish individual species. We developed a liquid-chromatography/tandem mass-spectrometry (LC-MS/MS) method to quantify eighteen phosphoethanolamine plasmalogens in RBCs to diagnose PBD patients, especially RCDP. Validation results showed a specific, robust, and precise method with broad analytical range. Age-specific reference intervals were established; control me-dians were used to assess plasmalogen deficiency in patients' RBCs. Clinical utility was also confirmed in Pex7 deficient mouse models recapitulating severe and milder RCDP clinical phenotypes. To our knowledge, this is the first attempt to replace the GC-MS method in the clinical laboratory. In addition to diagnosing PBDs, structure-specific plasmalogen quantitation could help understand disease pathogenesis and monitor therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据