Bargui Rezlène, Solgadi Audrey, Dumont Florent, Prost Bastien, Vadrot Nathalie, Filipe Anne, Ho Andrew T V, Ferreiro Ana, Moulin Maryline
Basic and Translational Myology Laboratory, Université Paris Cité, BFA, CNRS UMR8251, F-75013 Paris, France.
UMS-IPSIT-SAMM, Université Paris-Saclay, INSERM, CNRS, Ingénierie et Plateformes au Service de l'Innovation Thérapeutique, F-91400 Orsay, France.
Biomedicines. 2023 Jan 17;11(2):234. doi: 10.3390/biomedicines11020234.
Growing evidence shows that the lipid bilayer is a key site for membrane interactions and signal transduction. Surprisingly, phospholipids have not been widely studied in skeletal muscles, although mutations in genes involved in their biosynthesis have been associated with muscular diseases. Using mass spectrometry, we performed a phospholipidomic profiling in the diaphragm of male and female, young and aged, wild type and knock-out mice, the murine model of an early-onset inherited myopathy with severe diaphragmatic dysfunction. We identified 191 phospholipid (PL) species and revealed an important sexual dimorphism in PLs in the diaphragm, with almost 60% of them being significantly different between male and female animals. In addition, 40% of phospholipids presented significant age-related differences. Interestingly, SELENON protein absence was responsible for remodeling of 10% PL content, completely different in males and in females. Expression of genes encoding enzymes involved in PL remodeling was higher in males compared to females. These results establish the diaphragm PL map and highlight an important PL remodeling pattern depending on sex, aging and partly on genotype. These differences in PL profile may contribute to the identification of biomarkers associated with muscular diseases and muscle aging.
越来越多的证据表明，脂质双层是膜相互作用和信号转导的关键位点。令人惊讶的是，尽管参与其生物合成的基因突变与肌肉疾病有关，但磷脂在骨骼肌中尚未得到广泛研究。我们使用质谱法，对雄性和雌性、年轻和年老、野生型和基因敲除小鼠（一种早发性遗传性肌病伴严重膈肌功能障碍的小鼠模型）的膈肌进行了磷脂组学分析。我们鉴定出191种磷脂（PL）种类，并揭示了膈肌中磷脂存在重要的性别二态性，其中近60%在雄性和雌性动物之间存在显著差异。此外，40%的磷脂呈现出与年龄相关的显著差异。有趣的是，SELENON蛋白缺失导致10%的磷脂含量重塑，在雄性和雌性中完全不同。与雌性相比，参与磷脂重塑的编码酶的基因在雄性中表达更高。这些结果建立了膈肌磷脂图谱，并突出了一种重要的磷脂重塑模式，该模式取决于性别、年龄，部分取决于基因型。磷脂谱的这些差异可能有助于识别与肌肉疾病和肌肉衰老相关的生物标志物。
