Renal sulfatides: sphingoid base-dependent localization and region-specific compensation of CerS2-dysfunction |
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Authors: | Christian Marsching Mariona Rabionet Daniel Mathow Richard Jennemann Christiane Kremser Stefan Porubsky Christian Bolenz Klaus Willecke Hermann-Josef Gr?ne Carsten Hopf Roger Sandhoff |
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Institution: | 2. Lipid Pathobiochemistry Group within Department of Cellular and Molecular Pathology;4. German Cancer Research Center (DKFZ), Heidelberg, Germany;11. Molecular Genetics, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany;8. Departments of Pathology and Urology;112. Instrumental Analytics and Bioanalytics, Mannheim University of Applied Sciences, Mannheim, Germany |
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Abstract: | Mammalian kidneys are rich in sulfatides. Papillary sulfatides, especially, contribute to renal adaptation to chronic metabolic acidosis. Due to differences in their ceramide (Cer) anchors, the structural diversity of renal sulfatides is large. However, the underling biological function of this complexity is not understood. As a compound’s function and its tissue location are intimately connected, we analyzed individual renal sulfatide distributions of control and Cer synthase 2 (CerS)2-deficient mice by imaging MS (IMS) and by LC-MS2 (in controls for the cortex, medulla, and papillae separately). To explain locally different structures, we compared our lipid data with regional mRNA levels of corresponding anabolic enzymes. The combination of IMS and in source decay-LC-MS2 analyses revealed exclusive expression of C20-sphingosine-containing sulfatides within the renal papillae, whereas conventional C18-sphingosine-containing compounds were predominant in the medulla, and sulfatides with a C18-phytosphingosine were restricted to special cortical structures. CerS2 deletion resulted in bulk loss of sulfatides with C23/C24-acyl chains, but did not lead to decreased urinary pH, as previously observed in sulfatide-depleted kidneys. The reasons may be the almost unchanged C22-sulfatide levels and constant total renal sulfatide levels due to compensation with C16- to C20-acyl chain-containing compounds. Intriguingly, CerS2-deficient kidneys were completely depleted of phytosphingosine-containing cortical sulfatides without any compensation. |
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Keywords: | ceramide synthase 2 imaging mass spectrometry liquid chromatography matrix-assisted laser desorption/ionization-time-of-flight electrospray ionization-mass spectrometry tandem mass spectrometry galactosylceramide I3-sulfate lactosylceramide II3-sulfate cortex medulla papillae sphingosine serine palmitoyl-coenzyme A transferase small subunits in source decay knockout |
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