Department of Chemistry, Yonsei University, Seoul, 03722, Korea.
College of Veterinary Medicine, BK21 Program for Veterinary Science and Research, Institute of Veterinary Science, Seoul National University, Seoul, 08826, Korea.
Sci Rep. 2017 Jun 12;7(1):3302. doi: 10.1038/s41598-017-02065-9.
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.
肿瘤抑制因子 p53 已知与骨骼肌中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，因此研究与 p53 相关的能量生成代谢与脂质谱的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 敲除（KO）小鼠的两种不同骨骼肌组织（比目鱼肌和跖肌）中的 329 种脂质（在鉴定出的 412 种脂质中）进行了定量分析。总的来说，在大多数脂质图谱中，p53 KO 对跖肌组织的脂质影响大于比目鱼肌。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）、神经鞘磷脂（SM）和三酰基甘油（TAG），包括 6 种 TAG（44:2、46:0、58:5、58:8、58:9 和 50:0），仅在跖肌组织中增加了 1.4-2 倍（p<0.05）。总的单半乳糖神经酰胺（MHC）水平，包括 3 种 MHC 物种（d18:0/24:0、d18:1/22:0 和 d18:1/24:0），仅在比目鱼肌组织中增加了 2-4 倍（p<0.05）。这些结果表明，在肌肉组织中缺乏 p53 会显著改变脂质谱。
