Global Changes in Lipid Profiles of Mouse Cortex, Hippocampus, and Hypothalamus Upon p53 Knockout.
Comprehensive lipidomic profiling in three different brain tissues (cortex, hippocampus, and hypothalamus) of mouse with p53 deficiency was performed by nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS/MS) and the profile was compared with that of the wild type. p53 gene is a well-known tumour suppressor that prevents genome mutations that can cause cancers. More than 300 lipids (among 455 identified species), including phospholipids (PLs), sphingolipids, ceramides (Cers), and triacylglycerols (TAGs) were quantitatively analysed by selective reaction monitoring (SRM) of nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (nUPLC-ESI-MS/MS). Among the three different neural tissues, hypothalamus demonstrated the most evident lipid profile changes upon p53 knockout. Alterations of PLs containing acyl chains of docosahexaenoic acid and arachidonic acid (highly enriched polyunsaturated fatty acids in the nervous system) were examined in relation to cell apoptosis upon p53 knockout. Comparison between sphingomyelins (SMs) and Cers showed that the conversion of SM to Cer did not effectively progress in the hypothalamus, resulting in the accumulation of SMs, possibly due to the inhibition of apoptosis caused by the lack of p53. Furthermore, TAGs were considerably decreased only in the hypothalamus, indicative of lipolysis that led to substantial weight loss of adipose tissue and muscles.
Department of Chemistry, Yonsei University, Seoul 03722, Korea.
Sang Tak
ST
Lee
Department of Chemistry, Yonsei University, Seoul 03722, Korea.
Jong Cheol
JC
Lee
College of Veterinary Medicine, BK21 Program for Veterinary Science and Research, Institute of Veterinary Science, Seoul National University, Seoul 08826, Korea.|Korea Mouse Phenotyping Center (KMPC), Seoul 08826, Korea.
Jong Whi
JW
Kim
College of Veterinary Medicine, BK21 Program for Veterinary Science and Research, Institute of Veterinary Science, Seoul National University, Seoul 08826, Korea.|Korea Mouse Phenotyping Center (KMPC), Seoul 08826, Korea.
Soo Young
SY
Cho
College of Veterinary Medicine, BK21 Program for Veterinary Science and Research, Institute of Veterinary Science, Seoul National University, Seoul 08826, Korea.|Korea Mouse Phenotyping Center (KMPC), Seoul 08826, Korea.
Je Kyung
JK
Seong
Department of Chemistry, Yonsei University, Seoul 03722, Korea.
Myeong Hee
MH
Moon
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008055:Lipids / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010743:Phospholipids / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D008055:Lipids; D010743:Phospholipids; D013107:Sphingolipids; D014280:Triglycerides; D016159:Tumor Suppressor Protein p53