Promotion of plasmalogen biosynthesis reverse lipid changes in a Barth Syndrome cell model
Promotion of plasmalogen biosynthesis reverse lipid changes in a Barth Syndrome cell model
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DOI：
10.1016/j.bbalip.2020.158677
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发表时间：
2020-06-01
影响因子：
4.8
通讯作者：
Epand, Richard M.
中科院分区：
文献类型：
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作者：
Bozelli, Jose Carlos;Lu, Daniel;Epand, Richard M.
在Barth综合征（BTHS）中，他法津突变导致心磷脂（CL）的数量和分子种类的变化，这是BTHS的标志。与BTHS相关CL的公认改变相反，最近在Barth标本中发现了缩醛磷脂水平的显著降低。为了恢复缩醛原水平，本研究报告了促进缩醛原生物合成对来自Barth患者的淋巴母细胞的脂质体以及对细胞活力、线粒体生物合成和线粒体膜电位的影响。高分辨率P-31 NMR磷脂组学分析表明，血浆乙醇胺（淋巴母细胞中的主要缩醛磷脂原）的水平增加，达到了与对照组相当的值，其二酰基-PE对应物的水平代偿性降低。重要的是，P-31 NMR显示CL水平显著增加，而不改变单溶血心磷脂的水平。质谱测量结果表明，血浆酶原生物合成的促进并没有改变目标磷脂的分子种类谱。此外，促进缩醛磷脂的生物合成并不影响细胞活力，虽然它显着减少线粒体拷贝数和恢复线粒体膜电位。总体而言，结果显示了促进缩醛磷脂生物合成对增加BTHS细胞模型中的CL水平的功效，并突出了补充有缩醛磷脂前体的饮食对BTHS患者的潜在有益作用。
In Barth syndrome (BTHS) mutations in tafazzin leads to changes in both the quantities and the molecular species of cardiolipin (CL), which are the hallmarks of BTHS. Contrary to the well-established alterations in CL associated with BTHS; recently a marked decrease in the plasmalogen levels in Barth specimens has been identified. To restore the plasmalogen levels, the present study reports the effect of promotion of plasmalogen biosynthesis on the lipidome of lymphoblasts derived from Barth patients as well as on cell viability, mitochondria biogenesis, and mitochondrial membrane potential. High resolution P-31 NMR phospholipidomic analysis showed an increase in the levels of plasmenylethanolamine (the major plasmalogen in lymphoblasts), which reached values comparable to the control and a compensatory decrease in the levels of its diacyl-PE counterpart. Importantly, P-31 NMR showed a significant increase in the levels of CL, while not altering the levels of monolysocardiolipin. Mass spectrometry measurements showed that the promotion of plasmalogen biosynthesis did not change the molecular species profile of targeted phospholipids. In addition, promotion of plasmalogen biosynthesis did not impact on cellular viability, although it significantly decrease mitochondria copy number and restored mitochondrial membrane potential. Overall, the results showed the efficacy of the promotion of plasmalogen biosynthesis on increasing the CL levels in a BTHS cell model and highlight the potential beneficial effect of a diet supplemented with plasmalogen precursors to BTHS patients.