MALDI reveals membrane lipid profile reversion in MDX mice.
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.
Benabdellah
Farida
F
Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, Av. de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
Yu
Hua
H
Brunelle
Alain
A
Laprévote
Olivier
O
De La Porte
Sabine
S
D000818:Animals; D008563:Membrane Lipids / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism; D010713:Phosphatidylcholines / Q000032:analysis / Q000737:chemistry; D012038:Regeneration / Q000502:physiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D008563:Membrane Lipids; D010713:Phosphatidylcholines