title: On-tissue localization of ceramides and other sphingolipids by MALDI mass spectrometry imaging.
abstract: A novel MALDI-FTICR imaging mass spectrometry (MALDI-IMS) workflow is described for on-tissue detection, spatial localization, and structural confirmation of low abundance bioactive ceramides and other sphingolipids. Increasingly, altered or elevated levels of sphingolipids, sphingolipid metabolites, and sphingolipid metabolizing enzymes have been associated with a variety of disorders such as diabetes, obesity, lysosomal storage disorders, and cancer. Ceramide, which serves as a metabolic hub in sphingolipid metabolism, has been linked to cancer signaling pathways and to metabolic regulation with involvement in autophagy, cell-cycle arrest, senescence, and apoptosis. Using kidney tissues from a new Farber disease mouse model in which ceramides of all acyl chain lengths and other sphingolipid metabolites accumulate in tissues, specific ceramides and sphingomyelins were identified by on-tissue isolation and fragmentation, coupled with an on-tissue digestion by ceramidase or sphingomyelinase. Multiple glycosphingolipid species were also detected. The newly generated library of sphingolipid ions was then applied to MALDI-IMS of human lung cancer tissues. Multiple tumor specific ceramide and sphingomyelin species were detected and confirmed by on-tissue enzyme digests and structural confirmation. High-resolution MALDI-IMS in combination with novel on-tissue ceramidase and sphingomyelinase enzyme digestions makes it now possible to rapidly visualize the distribution of bioactive ceramides and sphingomyelin in tissues.
authors: Department of Cell and Molecular Pharmacology and MUSC Proteomics Center, Medical University of South Carolina , 173 Ashley Avenue, Charleston, South Carolina 29425, United States.
authors: E Ellen
authors: EE
authors: Jones
authors: Shaalee
authors: S
authors: Dworski
authors: Daniel
authors: D
authors: Canals
authors: Josefina
authors: J
authors: Casas
authors: Gemma
authors: G
authors: Fabrias
authors: Drew
authors: D
authors: Schoenling
authors: Thierry
authors: T
authors: Levade
authors: Chadrick
authors: C
authors: Denlinger
authors: Yusuf A
authors: YA
authors: Hannun
authors: Jeffrey A
authors: JA
authors: Medin
authors: Richard R
authors: RR
authors: Drake
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000473:pathology; D045744:Cell Line, Tumor; D002518:Ceramides / Q000032:analysis*; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology; D051379:Mice; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D013107:Sphingolipids / Q000032:analysis*; D057188:Workflow
chemical_list: D002518:Ceramides; D013107:Sphingolipids