MALDI reveals membrane lipid profile reversion in MDX mice
MALDI reveals membrane lipid profile reversion in MDX mice
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DOI：
10.1016/j.nbd.2009.07.013
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发表时间：
2009-11-01
影响因子：
6.1
通讯作者：
De La Porte, Sabine
中科院分区：
文献类型：
--
作者：
Benabdellah, Farida;Yu, Hua;De La Porte, Sabine
杜氏肌营养不良症（DMD）是最常见和严重的X连锁肌病，其特征是缺乏肌营养不良蛋白（一种正常肌肉功能所需的肌膜下蛋白）。在先前通过原位基质辅助激光解吸电离质谱法（MALDI-MS）对营养不良（mdx）小鼠（DMD的动物模型）的骨骼肌的脂质含量进行的研究中，在变性（异常纤维形态）和结构化（正常纤维形态）之间观察到磷脂酰胆碱PC 34：2/PC 34：1离子峰强度比的反转。一种可能的治疗这种戏剧性的疾病是引入外源性一氧化氮（NO）供体到生物体，导致utrophin的增加和营养不良表型的回归。在目前的工作中，通过串联质谱法确认这两种磷脂的结构后，其强度比反转被用来证明恢复的膜脂质组合物非常相似的野生型小鼠的mdx小鼠与吗西多明，NO供体的治疗后。这与通过免疫组织学观察到的小鼠再生过程增加有关。(C)2009 Elsevier Inc. All rights reserved.
Duchenne muscular dystrophy (DMD), the most common and severe X-linked myopathy, is characterized by the lack of dystrophin, a sub-sarcolemmal protein necessary for normal muscle functions. In a previous study of the lipid content of skeletal muscles of dystrophic (mdx) mice, the animal model for DMD, by in situ Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry (MALDI-MS), an inversion of the phosphatidylcholine PC34:2/PC34:1 ion peaks intensity ratio was observed between destructured (abnormal fiber morphology) and structured (normal fiber morphology). A possible treatment for this dramatic disease is to introduce an exogenous nitric oxide (NO) donor into the organism, leading to an increase of utrophin and a regression of the dystrophic phenotype. In the present work, after confirmation by tandem mass spectrometry of the structure of these two phospholipids, their intensity ratio inversion was used to evidence a restoration of membrane lipid composition very similar to those of wild-type mice after the treatment of mdx mice with molsidomine, a NO donor. This was associated with the observation by immunohistology of an increase of the regeneration process in the mice. (C) 2009 Elsevier Inc. All rights reserved.