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Expression of Ceramide Synthases in Mice and Their Roles in Regulating Acyl-Chain Sphingolipids: A Framework for Baseline Levels and Future Implications in Aging and Disease.
Richardson, Whitney J; Humphrey, Sophia B; Sears, Sophia M; Hoffman, Nicholas A; Orwick, Andrew J; Doll, Mark A; Doll, Chelsea L; Xia, Catherine; Hernandez-Corbacho, Maria; Snider, Justin M; Obeid, Lina M; Hannun, Yusuf A; Snider, Ashley J; Siskind, Leah J.
Afiliación
  • Richardson WJ; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Humphrey SB; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Sears SM; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Hoffman NA; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Orwick AJ; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Doll MA; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Doll CL; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Xia C; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Hernandez-Corbacho M; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Snider JM; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Obeid LM; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Hannun YA; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Snider AJ; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
  • Siskind LJ; Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky (W.J.R., S.B.H., S.M.S., N.A.H., A.J.O., M.A.D., L.J.S.); Department of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York (M.H.-C
Mol Pharmacol ; 105(3): 131-143, 2024 Feb 15.
Article en En | MEDLINE | ID: mdl-38164625
ABSTRACT
Sphingolipids are an important class of lipids present in all eukaryotic cells that regulate critical cellular processes. Disturbances in sphingolipid homeostasis have been linked to several diseases in humans. Ceramides are central in sphingolipid metabolism and are largely synthesized by six ceramide synthase (CerS) isoforms (CerS1-6), each with a preference for different fatty acyl chain lengths. Although the tissue distribution of CerS mRNA expression in humans and the roles of CerS isoforms in synthesizing ceramides with different acyl chain lengths are known, it is unknown how CerS expression dictates ceramides and downstream metabolites within tissues. In this study, we analyzed sphingolipid levels and CerS mRNA expression in 3-month-old C57BL/6J mouse brain, heart, kidney, liver, lung, and skeletal muscle. The results showed that CerS expression and sphingolipid species abundance varied by tissue and that CerS expression was a predictor of ceramide species within tissues. Interestingly, although CerS expression was not predictive of complex sphingolipid species within all tissues, composite scores for CerSs contributions to total sphingolipids measured in each tissue correlated to CerS expression. Lastly, we determined that the most abundant ceramide species in mouse tissues aligned with CerS mRNA expression in corresponding human tissues (based on chain length preference), suggesting that mice are relevant preclinical models for ceramide and sphingolipid research. SIGNIFICANCE STATEMENT The current study demonstrates that ceramide synthase (CerS) expression in specific tissues correlates not only with ceramide species but contributes to the generation of complex sphingolipids as well. As many of the CerSs and/or specific ceramide species have been implicated in disease, these studies suggest the potential for CerSs as therapeutic targets and the use of sphingolipid species as diagnostics in specific tissues.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxidorreductasas / Esfingolípidos / Ceramidas Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Infant Idioma: En Revista: Mol Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxidorreductasas / Esfingolípidos / Ceramidas Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Infant Idioma: En Revista: Mol Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos