Sulfatide with ceramide composed of phytosphingosine (t18:0) and 2-hydroxy FAs in renal intercalated cells

Nakashima, Keiko; Hirahara, Yukie; Koike, Taro; Tanaka, Susumu; Gamo, Keizo; Oe, Souichi; Hayashi, S.; Seki-Omura, Ryohei; Nakano, Yuusuke; Ohe, Chisato; Yoshida, Takashi; Kataoka, Yosky; Tsuda, Masayuki; Yamashita, Tsuneo; Honke, Koichi; Kitada, Masaaki

doi:10.1016/j.jlr.2022.100210

Cited by 7 publications

(5 citation statements)

References 61 publications

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“…1i and j ; Supplementary Fig. 10 for sulfatide metabolism), where they are known to be critical for urinary pH and ammonium excretion and have been characterized at single intercalated cell level 35, 39 .…”

Section: Resultsmentioning

confidence: 99%

“…In these mice, sulfatides, a family of sulfated glycosphingolipids, selectively accumulate in kidneys and other organs [26][27][28] . Because of this wellunderstood biology of ARSA-/-mice, we could use kidney sulfatides, whose masses, chemical sum formulae and structures (but not their quantities) are known, as qualitative ground truth for statistical evaluation of IRI-guided MSI methods, for method validation and for benchmarking against 4D LC-TIMS-MS sulfatide lipidomics, against previous sulfatide MSI studies and against CCS value prediction models 26,[28][29][30][31][32][33][34][35][36][37][38][39][40][41] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Deep MALDI-MS Spatial ‘Omics guided by Quantum Cascade Laser Mid-infrared Imaging Microscopy

Gruber,

Schmidt,

Enzlein

et al. 2023

Preprint

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In spatial ‘omics, highly confident molecular identifications are indispensable for the investigation of complex biology and for spatial biomarker discovery. However, current mass spectrometry (MS)-based spatial ‘omics must compromise between data acquisition speed and biochemical profiling depth, thus often leading to only “putative” molecular identifications. Here, we introduce fast quantum cascade laser mid-infrared imaging microscopy to guide MS imaging to confined tissue areas of high interest,e.g.,multicellular spheroid cores or kidney glomeruli, for spatial lipidomics profiling at maximized analytical depth utilizing magnetic resonance-MS imaging at >106resolution or prm-PASEF-MS2fragmentation imaging. Instigating selective sulfatide accumulation in arylsulfatase A-deficient mice as ground truth concept, we demonstrate that deep QCL-infrared-guidedon-tissuespatial ‘omics unequivocally identifies 120 sulfatides. This approach enables identifications of odd-chain sulfatides and studies of structure-ion mobility-relationships that provide chemical rationales for improvements to current ion mobility prediction algorithms. Workflows and data processing tools are provided as community resources.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deep MALDI-MS Spatial ‘Omics guided by Quantum Cascade Laser Mid-infrared Imaging Microscopy

Gruber,

Schmidt,

Enzlein

et al. 2023

Preprint

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“…Studies of CERT specificity for ceramides having different acyl groups indicated that those having a long-chain α-hydroxy fatty acid were transported by CERT more efficiently than those with non-hydroxylated ones [ 11 ]. Additional support for these observations is provided by the findings that α-OH fatty acids are found in Gal-Cer-containing GSLs such as sulfatide [ 92 ] and GM4 [ 93 ]. After the conversion of Cer transported to the cis-Golgi to Glc-Cer, it is carried by a member of the glycolipid transport protein (GLTP) family [ 94 ] to the trans-Golgi.…”

Section: Role Of Ceramide Composition In Sphingolipid Transportmentioning

confidence: 94%

Sphingolipids: Less Enigmatic but Still Many Questions about the Role(s) of Ceramide in the Synthesis/Function of the Ganglioside Class of Glycosphingolipids

Schengrund

2024

IJMS

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While much has been learned about sphingolipids, originally named for their sphinx-like enigmatic properties, there are still many unanswered questions about the possible effect(s) of the composition of ceramide on the synthesis and/or behavior of a glycosphingolipid (GSL). Over time, studies of their ceramide component, the sphingoid base containing the lipid moiety of GSLs, were frequently distinct from those performed to ascertain the roles of the carbohydrate moieties. Due to the number of classes of GSLs that can be derived from ceramide, this review focuses on the possible role(s) of ceramide in the synthesis/function of just one GSL class, derived from glucosylceramide (Glc-Cer), namely sialylated ganglio derivatives, initially characterized and named gangliosides (GGs) due to their presence in ganglion cells. While much is known about their synthesis and function, much is still being learned. For example, it is only within the last 15–20 years or so that the mechanism by which the fatty acyl component of ceramide affected its transport to different sites in the Golgi, where it is used for the synthesis of Glu- or galactosyl-Cer (Gal-Cer) and more complex GSLs, was defined. Still to be fully addressed are questions such as (1) whether ceramide composition affects the transport of partially glycosylated GSLs to sites where their carbohydrate chain can be elongated or affects the activity of glycosyl transferases catalyzing that elongation; (2) what controls the differences seen in the ceramide composition of GGs that have identical carbohydrate compositions but vary in that of their ceramide and vice versa; (3) how alterations in ceramide composition affect the function of membrane GGs; and (4) how this knowledge might be applied to the development of therapies for treating diseases that correlate with abnormal expression of GGs. The availability of an updatable data bank of complete structures for individual classes of GSLs found in normal tissues as well as those associated with disease would facilitate research in this area.

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“…It is of note that it is one of only two phytosphingosine ceramides detected in the dataset and the only one positively correlated with an FTU. SHexCer(t18:0/h24:0) (m/z 924.639) has been reported to specifically localize to the collecting duct 36 . The presence of the collecting duct-specific 4-hydroxylated SHexCer(t18:0/h24:0) (m/z 924.639) in conjunction with long chain sphingomyelins, SM(40:0;2O) (m/z 805.679) and SM(42:0;3O) (m/z 833.711), which are two of the top collecting duct biomarker candidates (Figure 6, figures S45-48, and S140-141), points to a functional role in membrane structure for this group of lipids.…”

Section: Lipid Profiles Of Renal Functional Tissue Unitsmentioning

confidence: 99%

A Lipid Atlas of the Human Kidney

Neumann

Patterson

Tideman

et al. 2022

Preprint

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The need for deep molecular and spatial characterization of tissues is growing rapidly to study complex diseases and disorders, particularly in the context of relationships between the cellular and molecular architecture from single cells to functional and anatomical regions of tissue. The human kidney is composed of over 26 cell types that actively coordinate to form higher order structures, such as the nephron. It is not yet understood how these structures vary molecularly throughout a single organ or among organs within the human population. Towards this end, we have developed an extensive molecular and cellular atlas of the human kidney consisting of over 3 million cells comprising 75,000 functional units from 13 human patients, using a spatially registered and integrated suite of technologies consisting of imaging mass spectrometry, histological staining, autofluorescence microscopy, and multiplexed immunofluorescence to comprehensively probe centimeter-sized areas of tissue. Through this approach, the cellular organization and metabolomic profiles of glomeruli, proximal tubules, distal tubules, and collecting ducts were determined as well as their intra- and inter-patient variance. Relating these lipid profiles to canonical cell types allowed us to hypothesize the functional role of specific phospholipids that have not previously been described, particularly how they relate to differences in BMI and sex. These integrated data provide a valuable reference molecular atlas for kidney researchers and are publicly available through the NIH Human Biomolecular Atlas Program (https://portal.hubmapconsortium.org/).

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Sulfatide with ceramide composed of phytosphingosine (t18:0) and 2-hydroxy FAs in renal intercalated cells

Cited by 7 publications

References 61 publications

Deep MALDI-MS Spatial ‘Omics guided by Quantum Cascade Laser Mid-infrared Imaging Microscopy

Deep MALDI-MS Spatial ‘Omics guided by Quantum Cascade Laser Mid-infrared Imaging Microscopy

Sphingolipids: Less Enigmatic but Still Many Questions about the Role(s) of Ceramide in the Synthesis/Function of the Ganglioside Class of Glycosphingolipids

A Lipid Atlas of the Human Kidney

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