1.FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer's disease.
Di Gaudio F1, Indelicato S2, Monastero R3, Altieri GI4, Fayer F4, Palesano O4, Fontana M2, Cefalù AB4, Greco M4, Bongiorno D5, Indelicato S5, Aronica A3, Noto D4, Averna MR6. Anal Bioanal Chem. 2016 Mar;408(9):2215-26. doi: 10.1007/s00216-015-9229-6. Epub 2016 Jan 11.
Lipidomic analysis is able to measure simultaneously thousands of compounds belonging to a few lipid classes. In each lipid class, compounds differ only by the acyl radical, ranging between C10:0 (capric acid) and C24:0 (lignoceric acid). Although some metabolites have a peculiar pathological role, more often compounds belonging to a single lipid class exert the same biological effect. Here, we present a lipidomics workflow that extracts the tandem mass spectrometry data from individual files and uses them to group compounds into structurally homogeneous clusters by chemical structure hierarchical clustering analysis (CHCA). The case-to-control peak area ratios of the metabolites are then analyzed within clusters. We created two freely available applications to assist the workflow: FragClust to generate the tables to be subjected to CHCA, and TestClust to perform statistical analysis on clustered data. We used the lipidomics data from the plasma of Alzheimer's disease (AD) patients in comparison with healthy controls to test the workflow.
2.Defective ceramide synthases in mice cause reduced amplitudes in electroretinograms and altered sphingolipid composition in retina and cornea.
Brüggen B1, Kremser C2, Bickert A2, Ebel P2, Vom Dorp K3, Schultz K1, Dörmann P3, Willecke K2, Dedek K1,4. Eur J Neurosci. 2016 Apr 18. doi: 10.1111/ejn.13260. [Epub ahead of print]
Complex sphingolipids are strongly expressed in neuronal tissue and contain ceramides in their backbone. Ceramides are synthesized by six ceramide synthases (CerS1-6). Although it is known that each tissue has a unique profile of ceramide synthase expression and ceramide synthases are implicated in several neurodegenerative disorders, the expression of ceramide synthase isoforms was never investigated in the retina. Here, we demonstrate CerS1, CerS2 and CerS4 expression in mouse retina and cornea, with CerS4 ubiquitously expressed in all retinal neurons and Müller cells. To test whether ceramide synthase deficiency affects retinal function, we compared electroretinograms and retina morphology between wild-type and CerS1-, CerS2, and CerS4-deficient mice. Electroretinograms were strongly reduced in amplitude in ceramide synthase-deficient mice, suggesting that signaling in the outer retina is affected. However, the number of photoreceptors and cone outer segment length were unaltered and no changes in retinal layer thickness or synaptic structures were found.
3.Plasma Ceramides and Neuropsychiatric Symptoms of Alzheimer's Disease.
Xing Y1, Tang Y2, Zhao L1, Wang Q1, Qin W1, Zhang JL3, Jia J2. J Alzheimers Dis. 2016 Apr 12. [Epub ahead of print]
BACKGROUND: Various evidences have demonstrated the influences of ceramides on Alzheimer's disease (AD) pathogenesis. Furthermore, increased ceramides were also suggested to be related to cognitive decline. However, the association between ceramides and neuropsychiatric symptoms of AD remains unclear.
4.Serum sphingolipidomic analyses reveal an upregulation of C16- ceramide and sphingosine-1-phosphate in hepatocellular carcinoma.
Grammatikos G1,2, Schoell N2, Ferreirós N3, Bon D4, Herrmann E4, Farnik H2, Köberle V2, Piiper A2, Zeuzem S2, Kronenberger B2, Waidmann O2, Pfeilschifter J1. Oncotarget. 2016 Feb 26. doi: 10.18632/oncotarget.7741. [Epub ahead of print]
We have recently shown that major alterations of serum sphingolipid metabolites in chronic liver disease associate significantly with the stage of liver fibrosis in corresponding patients. In the current study we assessed via mass spectrometry serum concentrations of sphingolipid metabolites in a series of 122 patients with hepatocellular carcinoma (HCC) compared to an age- and sex-matched series of 127 patients with cirrhosis. We observed a highly significant upregulation of long and very long chain ceramides (C16-C24) in the serum of patients with HCC as compared to patients with cirrhosis (P < 0.001). Accordingly, dihydro-ceramides, synthetic precursors of ceramides and notably sphingosine, sphingosine-1-phosphate (S1P) and sphinganine-1-phosphate (SA1P) were upregulated in patients with HCC (P < 0.001). Especially the diagnostic accuracy of C16-ceramide and S1P, assessed by receiver operating curve (ROC) analysis, showed a higher area under the curve (AUC) value as compared to alpha fetoprotein (AFP) (0.