title: Renal sulfatides: sphingoid base-dependent localization and region-specific compensation of CerS2-dysfunction.
abstract: Mammalian kidneys are rich in sulfatides. Papillary sulfatides, especially, contribute to renal adaptation to chronic metabolic acidosis. Due to differences in their cer-amide (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-MS(2) (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-MS(2) 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.
authors.affiliation: Center for Applied Research "Applied Biomedical Mass Spectrometry" (ABIMAS), Mannheim, Germany Lipid Pathobiochemistry Group within Department of Cellular and Molecular Pathology German Cancer Research Center (DKFZ), Heidelberg, Germany Institute of Medical Technology, University of Heidelberg and Mannheim University of Applied Sciences, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Marsching
authors.affiliation: Lipid Pathobiochemistry Group within Department of Cellular and Molecular Pathology German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Mariona
authors.initials: M
authors.lastname: Rabionet
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mathow
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Jennemann
authors.affiliation: Molecular Genetics, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Kremser
authors.affiliation: Departments of Pathology and Urology.
authors.forename: Stefan
authors.initials: S
authors.lastname: Porubsky
authors.affiliation: University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.affiliation: Molecular Genetics, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.affiliation: Center for Applied Research "Applied Biomedical Mass Spectrometry" (ABIMAS), Mannheim, Germany German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.affiliation: Center for Applied Research "Applied Biomedical Mass Spectrometry" (ABIMAS), Mannheim, Germany Institute of Medical Technology, University of Heidelberg and Mannheim University of Applied Sciences, Mannheim, Germany Lipid Pathobiochemistry Group within Department of Cellular and Molecular Pathology.
authors.forename: Carsten
authors.initials: C
authors.lastname: Hopf
authors.affiliation: Center for Applied Research "Applied Biomedical Mass Spectrometry" (ABIMAS), Mannheim, Germany Lipid Pathobiochemistry Group within Department of Cellular and Molecular Pathology German Cancer Research Center (DKFZ), Heidelberg, Germany Instrumental Analytics and Bioanalytics, Mannheim University of Applied Sciences, Mannheim, Germany.
authors.forename: Roger
authors.initials: R
authors.lastname: Sandhoff
mesh_terms: D000818:Animals; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D057054:Molecular Imaging; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051102:Serine C-Palmitoyltransferase / Q000235:genetics; D051049:Sphingosine N-Acyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013433:Sulfoglycosphingolipids / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D013433:Sulfoglycosphingolipids; C580723:Cers2 protein, mouse; D051049:Sphingosine N-Acyltransferase; D051102:Serine C-Palmitoyltransferase; C541445:ssSPTa
keywords: ceramide synthase 2; cortex; electrospray ionization-mass spectrometry; galactosylceramide I3-sulfate; imaging mass spectrometry; in source decay; knockout; lactosylceramide II3-sulfate; liquid chromatography; matrix-assisted laser desorption/ionization-time-of-flight; medulla; papillae; serine palmitoyl-coenzyme A transferase small subunits; sphingosine; tandem mass spectrometry