Jeongah Oh, Sneha Muralidharan, Qing Zhao, Johannes Scholz, Iris D Zelnik, Shani Blumenreich, Tammar Joseph, Tamir Dingjan, Pradeep Narayanaswamy, Hyungwon Choi, Heiko Hayen, Federico Torta, Anthony H Futerman
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引用次数: 0
Abstract
The sphingolipidome contains thousands of structurally distinct sphingolipid (SL) species. This enormous diversity is generated by the combination of different long-chain bases (LCBs), N-acyl chains and head groups. In mammals, LCBs are N-acylated with different fatty acids (from C14 to C32, with different degrees of saturation) by six ceramide synthases (CerS1-6) to generate dihydroceramides (DHCer), with each CerS exhibiting specificity toward acyl-Coenzyme As of defined chain length. CerS2 synthesizes very-long chain dihydroceramide, and mice in which CerS2 has been deleted display a number of pathologies. We now expand previous analyses of the mouse sphingolipidome by examining 259 individual SL species in 18 different tissues, building an extensive SL tissue atlas of WT and CerS2 null mice. Although many of the changes in SL levels were similar to those reported earlier, a number of unexpected findings in CerS2 null mouse tissues were observed, such as the decrease in ceramide 1-phosphate levels in the brain, the increase in C26-SL levels in the lung, and no changes in levels of ceramides containing t18:0-LCBs (phytosphinganine). Furthermore, analysis of levels of other metabolites revealed changes in at least six major metabolic pathways, including some that impinge upon the SL metabolism. Together, these data highlight the complex changes that occur in the lipidome and metabolome upon depletion of CerS2, indicating how sphingolipids are connected to many other pathways and that care must be taken when assigning a relationship between tissue pathology and one or other specific SL species.
期刊介绍:
The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.