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Lipidomic analysis of skeletal muscle tissues of p53 knockout mice by nUPLC-ESI-MS/MS

机译:用nUPLC-ESI-MS / MS对p53基因敲除小鼠的骨骼肌组织进行血脂分析

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摘要

Tumour suppressor p53 is known to be associated with the maintenance of mitochondrial functional properties in the skeletal muscles. As deactivation or mutation of p53 can affect the synthesis of lipids, investigating the relationship between p53-related energy generation metabolism and perturbation of lipid profile is critical. In this study, 329 lipid species (among 412 identified species) in two different skeletal muscle tissues (the gastrocnemius and soleus) from p53 knockout (KO) mice were quantitatively analysed using nanoflow ultrahigh performance liquid chromatography tandem mass spectrometry (nUPLC-MS/MS). Overall, lipids from the soleus tissues were more affected by p53 KO than those from the gastrocnemius in most lipid profiles. In p53 KO, lysophosphatidylcholine (LPC), lysophosphatidylserine (LPS), phosphatidic acid (PA), sphingomyelin (SM), and triacylglycerol (TAG), including 6 TAG (44:2, 46:0, 58:5, 58:8, 58:9, and 50:0), were significantly increased (p < 0.05) by 1.4–2-fold only in the soleus tissue. Overall monohexosylceramide (MHC) levels, including those of 3 MHC species (d18:0/24:0, d18:1/22:0, and d18:1/24:0), were significantly increased (p < 0.05) by 2–4 fold, only in the gastrocnemius tissue. The results suggest that lipid profiles are significantly altered by the lack of p53 in muscle tissues.
机译:已知抑癌基因p53与骨骼肌线粒体功能特性的维持有关。由于p53的失活或突变会影响脂质的合成,因此研究p53相关的能量产生代谢与脂质分布紊乱之间的关系至关重要。在这项研究中,使用纳流超高效液相色谱串联质谱法(nUPLC-MS / MS)对来自p53基因敲除(KO)小鼠的两个不同骨骼肌组织(腓肠肌和比目鱼肌)中的329种脂质物种(腓肠肌和比目鱼肌)进行了定量分析。 )。总体而言,比目鱼腓肠肌的脂质在大多数脂质谱中比目鱼组织的脂质受p53 KO的影响更大。在p53 KO中,溶血磷脂酰胆碱(LPC),溶血磷脂酰丝氨酸(LPS),磷脂酸(PA),鞘磷脂(SM)和三酰基甘油(TAG),包括6个TAG(44:2、46:0、58:5、58:8 ,58:9和50:0)仅在比目鱼组织中显着增加(p <0.05)1.4-2倍。单己糖神经酰胺(MHC)的总体水平(包括3种MHC物种(d18:0/24:0,d18:1/22:0和d18:1/24:0)的水平)显着提高了(p <0.05)2 –4倍,仅在腓肠肌组织中。结果表明,由于肌肉组织中缺乏p53,脂质的分布显着改变。

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